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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2015-02022 | Registry Identifier | CTRP |
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The purpose of this study is to determine the maximum tolerated dose (MTD) of Pregnyl® when given in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk (Arm 1) or refractory/dependent (Arm 2) aGVHD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
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| Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
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| Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
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| Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pregnyl® | Drug | Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I: MTD (USP hCG) | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm^2). | Day 14 after initiation of protocol therapy |
| Phase I: MTD (pg EGF/m^2) | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/m^2). | Day 14 after initiation of protocol therapy |
| Number of Patients With Complete Response | Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD. | Day 28 after initiation of protocol therapy |
| Number of Patients With Partial Response | Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD. | Day 28 after initiation of protocol therapy |
| Number of Patients With Mixed Response | Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD. | Day 70 after initiation of protocol therapy |
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Inclusion Criteria:
Acute graft versus host disease (GVHD) fitting one of the following categories:
High-Risk aGVHD (ARM 1): Pediatric or adult (ages 12-76 years) HCT recipients with high-risk acute GVHD, as determined by the refined MN acute GVHD risk score: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3 or amphiregulin ≥ 33 pg/ml) or
Steroid-Refractory aGVHD (ARM 2): Pediatric or adult (ages 12-76 years) HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following:
Adequate organ function at study enrollment defined as:
Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)
Exclusion Criteria:
Screening Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shernan Holtan, MD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37279855 | Derived | Holtan SG, Hoeschen A, Cao Q, Ustun C, Betts BC, Jurdi NE, Maakaron J, Rashidi A, Miller JS, Wagner JE, Blazar BR, Jacobson PA, Panoskaltsis-Mortari A, Weisdorf DJ, MacMillan ML. Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease. Transplant Cell Ther. 2023 Aug;29(8):509.e1-509.e8. doi: 10.1016/j.jtct.2023.05.021. Epub 2023 Jun 4. | |
| 32236525 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG001 | Arm 1: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG002 | Arm 1: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG003 | Arm 1: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG004 | Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG005 | Arm 1: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG006 | Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG007 | Arm 1: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| FG008 | Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG009 | Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG010 | Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG011 | Arm 2A: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG012 | Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG013 | Arm 2A: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG014 | Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG015 | Arm 2A: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG016 | Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG017 | Arm 2A: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG018 | Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG019 | Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG020 | Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG021 | Arm 2B: Phase 2 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG022 | Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG023 | Arm 2B: Phase 2 Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG024 | Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG025 | Arm 2B: Phase 2 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG026 | Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG027 | Arm 2B: Phase 2 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG028 | Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG029 | Arm 2B: Phase 2 Dose Level 3 2,000 USP | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG030 | Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG031 | Arm 2B: Phase 2 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG032 | Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| FG033 | Arm 2B: Phase 2 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase I: MTD (USP hCG) | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm^2). | Posted | Number | Pregnyl dosage (USP hCG) | Day 14 after initiation of protocol therapy |
|
70 Days after first treatment
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| blood and lympathic system | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Shernan Holtan, MD | University of Minnesota, Masonic Cancer Center | (612) 626-5654 | sgholtan@umn.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 27, 2020 | Mar 15, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 20, 2020 | Mar 15, 2023 | ICF_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006063 | Chorionic Gonadotropin |
| ID | Term |
|---|---|
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Experimental |
Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2A: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2A: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2A: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level -2: 125 USP hCG/875 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase I Dose Level -1: 250 USP hCG/1,750 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Experimental | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. |
|
| Arm 1: Phase 2 MTD | Experimental | After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low |
|
| Arm 2A: MTD | Experimental | After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low |
|
| Arm 2B: MTD | Experimental | After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low |
|
|
|
| Day 28 after initiation of protocol therapy |
| Number of Patients With No Response | Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved. | Day 28 after initiation of protocol therapy |
| Number of Participants With Incidence of aGVHD Flare | Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28. | Day 28 after initiation of protocol therapy |
| Number of Participants With Incidence of aGVHD Flare | Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 56. | Day 56 after initiation of protocol therapy |
| Rate of Participants Who Fail Treatment at Day 28 | Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls. | Day 28 after initiation of protocol therapy |
| Rate of Participants Who Fail Treatment at Day 56 | Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls. | Day 56 after initiation of protocol therapy |
| Derived |
| Holtan SG, Hoeschen AL, Cao Q, Arora M, Bachanova V, Brunstein CG, Miller JS, Rashidi A, Slungaard A, Ustun C, Vercellotti GM, Warlick ED, Betts BC, El Jurdi N, He F, Chen C, Gandhi I, Wagner JE, Blazar BR, Jacobson PA, Shabaneh A, Wang J, Panoskaltsis-Mortari A, MacMillan ML, Weisdorf DJ. Facilitating resolution of life-threatening acute GVHD with human chorionic gonadotropin and epidermal growth factor. Blood Adv. 2020 Apr 14;4(7):1284-1295. doi: 10.1182/bloodadvances.2019001259. |
| BG001 | Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG002 | Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG003 | Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG004 | Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG005 | Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG006 | Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG007 | Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG008 | Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG009 | Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG010 | Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG011 | Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG012 | Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| BG013 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | 2a: Steroid-Dependent aGVHD | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
| OG002 | 2b: Steroid-Refractory aGVHD | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. |
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| Primary | Phase I: MTD (pg EGF/m^2) | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/m^2). | Posted | Number | Pregnyl dosage (pg EGF/m^2) | Day 14 after initiation of protocol therapy |
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| Primary | Number of Patients With Complete Response | Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Primary | Number of Patients With Partial Response | Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Primary | Number of Patients With Mixed Response | Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Primary | Number of Patients With No Response | Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Secondary | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD. | Posted | Count of Participants | Participants | Day 70 after initiation of protocol therapy |
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| Secondary | Number of Participants With Incidence of aGVHD Flare | Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Secondary | Number of Participants With Incidence of aGVHD Flare | Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 56. | Posted | Number | participants | Day 56 after initiation of protocol therapy |
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| Secondary | Rate of Participants Who Fail Treatment at Day 28 | Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls. | Posted | Number | participants | Day 28 after initiation of protocol therapy |
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| Secondary | Rate of Participants Who Fail Treatment at Day 56 | Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls. | Posted | Number | participants | Day 56 after initiation of protocol therapy |
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| 0 |
| 2 |
| 1 |
| 2 |
| 1 |
| 2 |
| EG001 | Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 2 | 1 | 2 | 1 | 2 |
| EG002 | Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 9 | 1 | 9 | 3 | 9 |
| EG003 | Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 13 | 2 | 13 | 6 | 13 |
| EG004 | Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 1 | 1 | 1 | 1 | 1 |
| EG005 | Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 4 | 2 | 4 | 2 | 4 |
| EG006 | Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 8 | 4 | 8 | 5 | 8 |
| EG007 | Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 2 | 2 | 2 | 2 | 2 |
| EG008 | Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 1 | 1 | 1 | 1 | 1 |
| EG009 | Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 0 | 5 | 5 | 5 | 3 | 5 |
| EG010 | Arm 2B: Phase 2 Dose Level 3 2,000 USP | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG011 | Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 2 | 2 | 2 | 2 | 2 |
| EG012 | Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m | Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 | 3 | 3 | 3 | 1 | 3 |
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic perforation | Gastrointestinal disorders | Systematic Assessment |
|
| Duode0l obstruction | Gastrointestinal disorders | Systematic Assessment |
|
| Duode0l perforation | Gastrointestinal disorders | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointesti0l disorders - Other, | Gastrointestinal disorders | Systematic Assessment |
|
| Multi-organ failure | General disorders | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
|
| Gallbladder pain | Hepatobiliary disorders | Systematic Assessment |
|
| Hepatobiliary disorders - Other, | Hepatobiliary disorders | Systematic Assessment |
|
| Catheter related infection | Infections and infestations | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | Systematic Assessment |
|
| Infections and infestations - Other, | Infections and infestations | Systematic Assessment |
|
| Lung infection | Infections and infestations | Systematic Assessment |
|
| Peritoneal infection | Infections and infestations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | Systematic Assessment |
|
| Reversible posterior | Nervous system disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment |
|
| Ear and labyrinth disorders - Other, specify | Ear and labyrinth disorders | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | Systematic Assessment |
|
| Middle ear inflammation | Ear and labyrinth disorders | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | Systematic Assessment |
|
| Blurred vision | Eye disorders | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | Systematic Assessment |
|
| Dry eye | Eye disorders | Systematic Assessment |
|
| Photophobia | Eye disorders | Systematic Assessment |
|
| Watering eyes | Eye disorders | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic perforation | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Duodenal obstruction | Gastrointestinal disorders | Systematic Assessment |
|
| Duodenal perforation | Gastrointestinal disorders | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | Systematic Assessment |
|
| Hemorrhoidal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | Systematic Assessment |
|
| Lip pain | Gastrointestinal disorders | Systematic Assessment |
|
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Oral hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Rectal fistula | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Edema face | General disorders | Systematic Assessment |
|
| Edema limbs | General disorders | Systematic Assessment |
|
| Edema trunk | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Injection site reaction | General disorders | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | Systematic Assessment |
|
| Bladder infection | Infections and infestations | Systematic Assessment |
|
| Catheter related infection | Infections and infestations | Systematic Assessment |
|
| Conjunctivitis infective | Infections and infestations | Systematic Assessment |
|
| Encephalitis infection | Infections and infestations | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | Systematic Assessment |
|
| Hepatic infection | Infections and infestations | Systematic Assessment |
|
| Infections and infestations - Other, specify | Infections and infestations | Systematic Assessment |
|
| Lip infection | Infections and infestations | Systematic Assessment |
|
| Lung infection | Infections and infestations | Systematic Assessment |
|
| Periorbital infection | Infections and infestations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Creatinine increased | Investigations | Systematic Assessment |
|
| Electrocardiogram QT corrected interval prolonged | Investigations | Systematic Assessment |
|
| Fibrinogen decreased | Investigations | Systematic Assessment |
|
| INR increased | Investigations | Systematic Assessment |
|
| Investigations - Other, specify | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Concentration impairment | Nervous system disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Lethargy | Nervous system disorders | Systematic Assessment |
|
| Movements involuntary | Nervous system disorders | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
|
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | Systematic Assessment |
|
| Sinus pain | Nervous system disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Tremor | Nervous system disorders | Systematic Assessment |
|
| Agitation | Psychiatric disorders | Systematic Assessment |
|
| Confusion | Psychiatric disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Hallucinations | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Cystitis noninfective | Renal and urinary disorders | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hot flashes | Vascular disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Lymphedema | Vascular disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |