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| ID | Type | Description | Link |
|---|---|---|---|
| 1K08HL143189-01A1 | U.S. NIH Grant/Contract | View source | |
| 5P30CA008748 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Cancer Institute (NCI) | NIH |
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This is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.
The research team earlier hypothesized and demonstrated that tocilizumab could attenuate the incidence of acute GVHD (aGVHD) after myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) Allogeneic hematopoietic cell transplantation (alloHCT), using matched sibling or unrelated donor. In this study, the research team hypothesizes that longer term interleukin 6 (IL-6) inhibition through treatment with tocilizumab by repeated dosing would mediate a beneficial effect not only on the risk of aGVHD, but also on chronic GVHD. This will be achieved by administering an additional dose of tocilizumab at Day +100 post-alloHCT, besides the pretransplant dose, as done in our previous clinical trial, thereby providing total prophylaxis against both acute and chronic GVHD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus/Methotrexate/Tocilizumab | Experimental | Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus | Drug | Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Patients With GVHD/Relapse-free (GRFS) Survival | GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up. | Day 365 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William R Drobyski, MD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Froedtert Hospital | Milwaukee | Wisconsin | 53226 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36106394 | Result | Chhabra S, Szabo A, Clurman A, McShane K, Waters N, Eastwood D, Samanas L, Fei T, Armijo G, Abedin S, Longo W, Hari P, Hamadani M, Shah NN, Runaas L, Jerkins JH, Van den Brink M, Peled JU, Drobyski WR. Mitigation of gastrointestinal graft-versus-host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination. Haematologica. 2023 Jan 1;108(1):250-256. doi: 10.3324/haematol.2022.281309. No abstract available. |
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Thirty-one subjects signed consent, but two did not meet final eligibility criteria and were not enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tacrolimus/Methotrexate/Tocilizumab | Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels. Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion. Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-allogeneic hematopoietic cell transplantation. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tacrolimus/Methotrexate/Tocilizumab | Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels. Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion. Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-allogeneic hematopoietic cell transplantation. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | The Number of Patients With GVHD/Relapse-free (GRFS) Survival | GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up. | Posted | Count of Participants | Participants | Day 365 |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tacrolimus/Methotrexate/Tocilizumab | Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days). Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels. Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion. Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| William Drobyski, MD | Froedtert and the Medical College of Wisconsin | 414-805-6700 | wdrobyski@mcw.edu |
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| 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 | Sep 19, 2019 | Mar 27, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 28, 2020 | Mar 27, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D008727 | Methotrexate |
| C502936 | tocilizumab |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000630 | Aminopterin |
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|
| Methotrexate | Drug | Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion. |
|
|
| Tocilizumab | Drug | Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus. |
|
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 0 |
| 29 |
| 28 |
| 29 |
| 28 |
| 29 |
| Heart Failure | Cardiac disorders | CTCAE 5.0 | Systematic Assessment |
|
| Pericardial Tamponade | Cardiac disorders | CTCAE 5.0 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Fever | General disorders | CTCAE 5.0 | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE 5.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment | Fungal pneumonia |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hematoman | Vascular disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE 5.0 | Systematic Assessment |
|
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | CTCAE 5.0 | Systematic Assessment | Leukocytosis, <100,000/mm^3 |
|
| Dry eye | Eye disorders | CTCAE 5.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Rectal pain | Gastrointestinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE 5.0 | Systematic Assessment |
|
| General disorders - Other, specify | General disorders | CTCAE 5.0 | Systematic Assessment | Subdural Hematoma |
|
| Portal vein thrombosis | Hepatobiliary disorders | CTCAE 5.0 | Systematic Assessment |
|
| Cytomegalovirus infection reactivation | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE 5.0 | Systematic Assessment | ENTEROCOLITIS INFECTIOUS |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE 5.0 | Systematic Assessment | Enterococcus bacteremia |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE 5.0 | Systematic Assessment | E. Coli |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE 5.0 | Systematic Assessment | Rhinovirus |
|
| Skin infection | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | CTCAE 5.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Electrocardiogram QT corrected interval prolonged | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Tumor lysis syndrome | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Musculoskeletal and connective tissue disorders - Other, pecify | Musculoskeletal and connective tissue disorders | CTCAE 5.0 | Systematic Assessment | Generalized muscle weakness |
|
| Headache | Nervous system disorders | CTCAE 5.0 | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE 5.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE 5.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE 5.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE 5.0 | Systematic Assessment |
|
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| D011622 |
| Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |