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| Name | Class |
|---|---|
| Incyte Corporation | INDUSTRY |
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An open-label, Phase II trial designed to assess the recommended phase 2 dose (RP2D) of itacitinib in combination ECP and efficacy of the combination after 24 weeks of therapy. The trial will consist of two parts: Part One will assess the RP2D. For dose-finding purposes, the dose limiting toxicity (DLT) evaluation period will be defined as the time from the first dose of itacitinib lead-in (7-day lead-in) to the last day of cycle one combination therapy (Cycle one day 28).
Part Two will further describe and characterize the safety and efficacy of the regimen. The RP2D will be determined by a 3+3 dose de-escalation design. Should dose level one be deemed intolerable, enrollment will proceed at dose level -1. The RP2D will be affirmed according to the rules of the 3+3 dose de-escalation scheme. Once an RP2D has been confirmed, Part 2 will open as an expansion cohort.
As this study was terminated after enrolling three patients out of an anticipated target accrual of 58, Part Two of this study did not occur.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment: all patients | Experimental | Patients will self-administer itacitinib every morning regardless of food. ECP will be administered twice weekly on consecutive days for 8 weeks per institutional standards. At the end of 8 weeks of combination therapy, patients will start a standard ECP taper schedule and itacitinib will be continued at the assigned dose level. After six cycles of therapy, itacitinib may be tapered at the treating investigator's discretion as described below. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Itacitinib | Drug | All eligible patients will begin study therapy with approximately a week lead-in of itacitinib monotherapy at scheduled dose. Itacitinib will be taken daily at scheduled dose for a total of six cycles. Itacitinib may be tapered as deemed appropriate by the treating investigator. Patients will remain on study therapy as long as treatment discontinuation criteria are not met. Patients with Partial Response (PR) or better may continue itacitinib for up to 1 year. |
| Measure | Description | Time Frame |
|---|---|---|
| Count of Participants With a Dose-limiting Toxicity (DLT) During the DLT Evaluation Period. | Adverse events were assessed at each study visit from the first dose of itacitinib during the lead-in period (lead-in period = 5-10 days) until the last day of cycle one (each cycle = 28 days) of combination treatment with itacitinib and Extracorporeal Photopheresis (ECP). A DLT was defined as an Adverse Event (AE) that was 1) attributed as possibly, probably, or definitely related to itacitinib or to the combination of itacitinib and ECP, and 2) graded as "severe" or "life threatening" (grade 3 or 4) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. | up to 38 days |
| Count of Participants With a Response to Treatment at 24 Weeks of Treatment | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Count of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) During Study Treatment | Adverse events were assessed at each study visit per CTCAE v5 criteria. This objective counts the number of participants who experienced 1) any adverse event of any severity, or 2) any serious adverse event that was possibly, probably, or definitely related to itacitinib or to combination treatment with itacitinib and ECP. |
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Inclusion Criteria:
Topical or inhaled treatments for chronic GVHD are allowed. Any prior ECP treatments for the management of acute GVHD must have occurred > 4 weeks prior to the initiation of itacitinib treatment.
Able to swallow and retain oral medication.
Life expectancy > 24 weeks.
Karnofsky performance status ≥ 60
Evidence of myeloid and platelet engraftment:
Note: Use of growth factors and transfusion support is allowed during the study; however, growth factors and transfusion support to reach a minimum absolute neutrophil count (ANC) or platelet count for inclusion are not allowed within the 7 days before the screening laboratory assessment.
Adequate organ function as defined as:
Hepatic:
Renal:
---estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 as calculated using the Modification of Diet in Renal Disease formula or by the Cockcroft-Gault formula:
Coagulation:
Willingness to avoid pregnancy or father children based on the criteria below and as described in Section 5.4.2:
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
Note: Prior and concomitant use of Calcineurin-Inhibitors (CNIs) for prevention and treatment of acute GVHD, as well as topical/inhaled steroids, is acceptable.
Received prior Janus kinase (JAK) inhibitor therapy for any indication ≤ 4 weeks prior to Cycle 1 Day 1.
Patients with relapsed or progressive malignant disease or any post-transplant lymphoproliferative disease.
Chronic GVHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
Inability to swallow food or any condition of the upper gastrointestinal tract that precludes the administration of oral medications.
Any contraindication for extracorporeal photopheresis (ECP) per the treating investigator's discretion.
Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the subject.
Pregnant or currently breast-feeding. Note: INCB039110 is a Janus kinase 1 (JAK1) inhibitor with the potential for serious or life-threatening birth defects or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with INCB039110, breastfeeding should be discontinued if the mother is treated with INCB039110. These potential risks may also apply to other agents used in this study.
Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug and while on trial.
Use of any prohibited concomitant medications as described in Section 6.5. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.
Inadequate recovery from toxicity and/or complications from major surgery before starting therapy.
Unwillingness to be transfused with blood components during the study.
History of other malignancy (not including the underlying malignancy that was the indication for the transplant), with the following exceptions:
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
History of thromboembolic event within 1 month before study registration.
HIV-infected patients on effective antiretroviral therapy with an undetectable viral load within 6 months are eligible for this trial.
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg). Participants with negative HBsAg and positive total hepatitis B core antigen (HBc) antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibodies are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Serology results performed less than or equal to 6 months prior to the first planned dose of itacitinib are acceptable for determining eligibility.
Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug/treatment and attending required study visits; pose a significant risk to the participant; or interfere with the interpretation of study data.
Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations) per the investigator's assessment.
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| Name | Affiliation | Role |
|---|---|---|
| Catherine Lee, MD | Huntsman Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huntsman Cancer Institute at University of Utah | Salt Lake City | Utah | 84112 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment: All Participants (Dose Level 1, Starting Dose) | Participants will begin with a 5-10 lead-in period of self-administered itacitinib, after which they will continue itacitinib for 6 28 day cycles. Extracorporeal Photopheresis (ECP) will begin on Cycle 1 Day 1 after the lead-in period, and will be administered twice weekly on consecutive days for 8 weeks. At the end of 8 weeks (2 cycles) of combination therapy, participants will start a standard ECP taper schedule and itacitinib will be continued at the assigned dose level. After six cycles of therapy, itacitinib may be tapered at the treating investigator's discretion. Though this study was initially conceived as a dose de-escalation study, the study was terminated with three participants accrued, meaning all patients received the starting dose of 200 mg daily, days 1-28 per cycle, per the 3+3 dose de-escalation study design. Thus, only one treatment arm is appropriate in reporting study results. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment: All Participants | Participants will begin with a 5-10 lead-in period of self-administered itacitinib, after which they will continue itacitinib for 6 28 day cycles. Extracorporeal Photopheresis (ECP) will begin on Cycle 1 Day 1 after the lead-in period, and will be administered twice weekly on consecutive days for 8 weeks. At the end of 8 weeks (2 cycles) of combination therapy, participants will start a standard ECP taper schedule and itacitinib will be continued at the assigned dose level. After six cycles of therapy, itacitinib may be tapered at the treating investigator's discretion. |
| 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 | Count of Participants With a Dose-limiting Toxicity (DLT) During the DLT Evaluation Period. | Adverse events were assessed at each study visit from the first dose of itacitinib during the lead-in period (lead-in period = 5-10 days) until the last day of cycle one (each cycle = 28 days) of combination treatment with itacitinib and Extracorporeal Photopheresis (ECP). A DLT was defined as an Adverse Event (AE) that was 1) attributed as possibly, probably, or definitely related to itacitinib or to the combination of itacitinib and ECP, and 2) graded as "severe" or "life threatening" (grade 3 or 4) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. | Posted | Count of Participants | Participants | up to 38 days |
|
Collection of serious adverse events will begin at the initiation of study treatment and end 30 days after the last dose of study treatment or until new cancer treatment is initiated, whichever happens the soonest. For this study, actual treatment ranged from 181 days to 350 days with a median of 203 days.
Adverse events were reviewed with the participant and the investigator at every study visit. All adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, were collected.
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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 | Treatment: All Participants | Participants will begin with a 5-10 lead-in period of self-administered itacitinib, after which they will continue itacitinib for 6 28 day cycles. Extracorporeal Photopheresis (ECP) will begin on Cycle 1 Day 1 after the lead-in period, and will be administered twice weekly on consecutive days for 8 weeks. At the end of 8 weeks (2 cycles) of combination therapy, participants will start a standard ECP taper schedule and itacitinib will be continued at the assigned dose level. After six cycles of therapy, itacitinib may be tapered at the treating investigator's discretion. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung infection | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment | human metapneumovirus |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | CTCAE v5 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinicaltrials.gov/CTRP Specialist | Huntsman Cancer Institute/University of Utah | 8012136215 | IITDataManagement@hci.utah.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 | Jan 28, 2022 | May 24, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 23, 2022 | May 24, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
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| ID | Term |
|---|---|
| C000718170 | itacitinib |
| C000603457 | INCB039110 |
| D017893 | Photopheresis |
| ID | Term |
|---|---|
| D011701 | PUVA Therapy |
| D014467 | Ultraviolet Therapy |
| D010789 | Phototherapy |
| D013812 | Therapeutics |
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The RP2D will be determined by a 3+3 dose de-escalation design. Once an RP2D has been confirmed, Part 2 will open as an expansion cohort. (As this study was terminated after enrolling 3 patients, Part 2 of the planned study did not occur.)
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| Extracorporeal Photopheresis (ECP) | Device | ECP will begin after itacitinib lead in period. At the end of 8 weeks of combination therapy, patients will start a standard ECP taper schedule. Patients achieving PR or better after 6 cycles of itacitinib may continue treatment with itacitinib for up to 1 year. Thereafter, itacitinib may be tapered at the treating investigator's discretion. |
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|
| during study treatment - up to 1 year |
| Count of Participants With a Response to Treatment After One Year of Treatment | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after one year of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. | 1 year |
| Count of Participants With Failure Free Survival (FFS) at 24 Weeks and 1 Year | Failure Free Survival (FFS) is defined as the number of participants at 24 weeks and at 1 year who have not experienced treatment failure. Treatment failure is defined as the initiation of secondary therapy for chronic GVHD, malignancy relapse, or death from any cause. | 24 weeks and 1 year |
| Count of Participants Who Have Withdrawn All Immunosuppressants at 1 Year | Immunosuppressive therapy is common for participants with GVHD. This objective counts the number of participants who were able to discontinue all immunosuppressants by 1 year of treatment and follow-up. | 1 year |
| Count of Participants With a Response to Treatment at 24 Weeks of Treatment Stratified by Concurrent Prednisone Use | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. Participants were also evaluated for the amount of prednisone (or other steroids converted by prednisone equivalence) they were using at the time of the response. This outcome is the same as outcome # 2, but has been stratified by prednisone use. | 24 weeks |
| Mean Cumulative Prednisone Used up to 24 Weeks | This outcome assessed the cumulative amount of prednisone (or other steroids converted to prednisone equivalence) used by participants up to 24 weeks of treatment. | 24 weeks |
| Count of Participants With Organ-specific Responses at 24 Weeks | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluate 9 organ systems, and for each organ, defines changes in symptoms to qualify as a partial response (PR), complete response (CR), or progressive disease (PD) in that organ. In general, PR in an organ indicates partial improvement after prior involvement of that organ. CR indicates improvement to no symptoms after prior involvement. PD indicates worsening of symptoms in the organ system. Lack of response indicates that the organ system was involved at both baseline and 24 weeks, but did not improve or deteriorate sufficiently to qualify for PR, CR, or PD. No involvement/Not evaluable indicates that the organ system never had any GVHD symptoms or was not able to be evaluated. | 24 weeks |
| Count of Participants With Organ-specific Responses at 1 Year | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 1 year of treatment. The criteria evaluate 9 organ systems, and for each organ, defines changes in symptoms to qualify as a partial response (PR), complete response (CR), or progressive disease (PD) in that organ. In general, PR in an organ indicates partial improvement after prior involvement of that organ. CR indicates improvement to no symptoms after prior involvement. PD indicates worsening of symptoms in the organ system. Lack of response indicates that the organ system was involved at both baseline and 24 weeks, but did not improve or deteriorate sufficiently to qualify for PR, CR, or PD. No involvement indicates that the organ system never had any GVHD symptoms. | 1 year |
| Mean NIH Global GVHD Score at 24 Weeks | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. One data point in the criteria is an overall global rating of the participant's GVHD, ranging from 0 (no GVHD) to 3 (severe GVHD). The baseline global score is reported in the baseline characteristics. | 24 weeks |
| Duration of Response (DOR) | DOR was measured as the interval between the date of initial documentation of a response (PR or better), and the date of progression, start of a new therapy for chronic GVHD (cGVHD) (including corticosteroids), or death from any cause. | up to 1 year |
| Mean Clinician-evaluated GVHD Severity Score at 24 Weeks and 1 Year | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline, after 24 weeks of treatment, and after one year of treatment. One data point in the criteria is a general rating the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). The baseline severity score is reported in the baseline characteristics. | at 24 weeks and 1 year |
| Mean Participant-reported cGVHD Symptom Severity Score at 24 Weeks and at 1 Year | Participants were asked to rate their own symptoms for chronic graft versus host disease (cGVHD) severity per the NIH Consensus Development Project Criteria at baseline, after 24 weeks of treatment, and after one year of treatment. One data point in is a general rating of the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). The baseline severity score is reported in the baseline characteristics. | 24 weeks and 1 year |
| Count of Participants With Non-relapse Mortality (NRM) | NRM is defined as death due to causes other than a relapse of their primary hematologic disease. This outcome reports the number of participants who were deceased at 24 weeks and at 1 year after the start of treatment whose death meets the definition of NRM. | 24 weeks and 1 year |
| Count of Participants With Relapse at 24 Weeks and 1 Year | Relapse is defined as re-activation of the participant's primary hematologic malignancy after it has been in remission. This outcome reports the number of participants who had experienced relapse at 24 weeks and at 1 year after start of treatment. | 24 weeks and 1 year |
| Count of Participants Alive at 24 Weeks and 1 Year | This outcome measures overall survival (OS), meaning the number of participants who remain alive at 24 weeks and at 1 year from start of treatment. | 24 weeks and 1 year |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | 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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| Mean Baseline NIH Global GVHD Score | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline. This data point in the criteria is an overall global rating of the participant's GVHD, ranging from 0 (no GVHD) to 3 (severe GVHD). | Mean | Standard Deviation | score on a scale |
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| Mean clinician-assessed NIH GVHD severity score | Participants were assessed by the treating clinician for chronic graft versus host disease (cGVHD) symptom severity per the NIH Consensus Development Project Criteria at baseline. One data point in the criteria is a general rating the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). | Mean | Standard Deviation | score on a scale |
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| Mean participant-assessed NIH GVHD severity score | Participants were asked to rate their own symptoms for chronic graft versus host disease (cGVHD) severity per the NIH Consensus Development Project Criteria at baseline. One data point in is a general rating of the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). | Mean | Standard Deviation | score on a scale |
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| Primary | Count of Participants With a Response to Treatment at 24 Weeks of Treatment | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. | Posted | Count of Participants | Participants | 24 weeks |
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| Secondary | Count of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) During Study Treatment | Adverse events were assessed at each study visit per CTCAE v5 criteria. This objective counts the number of participants who experienced 1) any adverse event of any severity, or 2) any serious adverse event that was possibly, probably, or definitely related to itacitinib or to combination treatment with itacitinib and ECP. | Posted | Count of Participants | Participants | during study treatment - up to 1 year |
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| Secondary | Count of Participants With a Response to Treatment After One Year of Treatment | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after one year of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. | Only one participant was assessed at the one year time point. The others had discontinued treatment prior to that time point. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Count of Participants With Failure Free Survival (FFS) at 24 Weeks and 1 Year | Failure Free Survival (FFS) is defined as the number of participants at 24 weeks and at 1 year who have not experienced treatment failure. Treatment failure is defined as the initiation of secondary therapy for chronic GVHD, malignancy relapse, or death from any cause. | Posted | Count of Participants | Participants | 24 weeks and 1 year |
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| Secondary | Count of Participants Who Have Withdrawn All Immunosuppressants at 1 Year | Immunosuppressive therapy is common for participants with GVHD. This objective counts the number of participants who were able to discontinue all immunosuppressants by 1 year of treatment and follow-up. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Count of Participants With a Response to Treatment at 24 Weeks of Treatment Stratified by Concurrent Prednisone Use | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluates 9 organ systems, and then defines a partial response (PR) as at least one organ system with improvement since baseline and no worsening in other organs. Complete response (CR) is defined as an improvement in all affected organ systems to having no GVHD symptoms in any organ system. All responses must occur without any secondary systemic immunosuppressive therapy, and no malignancy recurrence or death. Participants with a PR or CR are counted as a response for this outcome. Participants were also evaluated for the amount of prednisone (or other steroids converted by prednisone equivalence) they were using at the time of the response. This outcome is the same as outcome # 2, but has been stratified by prednisone use. | Two participants, both at the 0 mg/kg/d prednisone use, were assessed for this measure at 24 weeks. The other had discontinued treatment prior to that time point. | Posted | Count of Participants | Participants | 24 weeks |
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| Secondary | Mean Cumulative Prednisone Used up to 24 Weeks | This outcome assessed the cumulative amount of prednisone (or other steroids converted to prednisone equivalence) used by participants up to 24 weeks of treatment. | Posted | Mean | Standard Deviation | milligrams | 24 weeks |
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| Secondary | Count of Participants With Organ-specific Responses at 24 Weeks | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. The criteria evaluate 9 organ systems, and for each organ, defines changes in symptoms to qualify as a partial response (PR), complete response (CR), or progressive disease (PD) in that organ. In general, PR in an organ indicates partial improvement after prior involvement of that organ. CR indicates improvement to no symptoms after prior involvement. PD indicates worsening of symptoms in the organ system. Lack of response indicates that the organ system was involved at both baseline and 24 weeks, but did not improve or deteriorate sufficiently to qualify for PR, CR, or PD. No involvement/Not evaluable indicates that the organ system never had any GVHD symptoms or was not able to be evaluated. | Posted | Count of Participants | Participants | 24 weeks |
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| Secondary | Count of Participants With Organ-specific Responses at 1 Year | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 1 year of treatment. The criteria evaluate 9 organ systems, and for each organ, defines changes in symptoms to qualify as a partial response (PR), complete response (CR), or progressive disease (PD) in that organ. In general, PR in an organ indicates partial improvement after prior involvement of that organ. CR indicates improvement to no symptoms after prior involvement. PD indicates worsening of symptoms in the organ system. Lack of response indicates that the organ system was involved at both baseline and 24 weeks, but did not improve or deteriorate sufficiently to qualify for PR, CR, or PD. No involvement indicates that the organ system never had any GVHD symptoms. | Only one participant completed 1 year of treatment to be evaluated for this outcome. | Posted | Count of Participants | Participants | 1 year |
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| Secondary | Mean NIH Global GVHD Score at 24 Weeks | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline and after 24 weeks of treatment. One data point in the criteria is an overall global rating of the participant's GVHD, ranging from 0 (no GVHD) to 3 (severe GVHD). The baseline global score is reported in the baseline characteristics. | Posted | Mean | Standard Deviation | score on a scale | 24 weeks |
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| Secondary | Duration of Response (DOR) | DOR was measured as the interval between the date of initial documentation of a response (PR or better), and the date of progression, start of a new therapy for chronic GVHD (cGVHD) (including corticosteroids), or death from any cause. | Two participants had a partial response or better. | Posted | Mean | Standard Deviation | days | up to 1 year |
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| Secondary | Mean Clinician-evaluated GVHD Severity Score at 24 Weeks and 1 Year | Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline, after 24 weeks of treatment, and after one year of treatment. One data point in the criteria is a general rating the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). The baseline severity score is reported in the baseline characteristics. | Only one participant continued treatment long enough to be evaluated at 1 year. | Posted | Mean | Standard Deviation | score on a scale | at 24 weeks and 1 year |
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| Secondary | Mean Participant-reported cGVHD Symptom Severity Score at 24 Weeks and at 1 Year | Participants were asked to rate their own symptoms for chronic graft versus host disease (cGVHD) severity per the NIH Consensus Development Project Criteria at baseline, after 24 weeks of treatment, and after one year of treatment. One data point in is a general rating of the severity of the participant's GVHD symptoms, ranging from 0 (GVHD symptoms not at all severe) to 10 (most severe GVHD symptoms possible). The baseline severity score is reported in the baseline characteristics. | One participant did not complete the cGVHD severity assessment at week 24. Two participants did not continue treatment long enough to self-assess for cGVHD severity at one year. | Posted | Mean | Standard Deviation | score on a scale | 24 weeks and 1 year |
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| Secondary | Count of Participants With Non-relapse Mortality (NRM) | NRM is defined as death due to causes other than a relapse of their primary hematologic disease. This outcome reports the number of participants who were deceased at 24 weeks and at 1 year after the start of treatment whose death meets the definition of NRM. | Posted | Count of Participants | Participants | 24 weeks and 1 year |
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|
| Secondary | Count of Participants With Relapse at 24 Weeks and 1 Year | Relapse is defined as re-activation of the participant's primary hematologic malignancy after it has been in remission. This outcome reports the number of participants who had experienced relapse at 24 weeks and at 1 year after start of treatment. | Posted | Count of Participants | Participants | 24 weeks and 1 year |
|
|
|
| Secondary | Count of Participants Alive at 24 Weeks and 1 Year | This outcome measures overall survival (OS), meaning the number of participants who remain alive at 24 weeks and at 1 year from start of treatment. | Posted | Count of Participants | Participants | 24 weeks and 1 year |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
|
| Watering eyes | Eye disorders | CTCAE v5 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE v5 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | CTCAE v5 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE v5 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v5 | Systematic Assessment |
|
| Chills | General disorders | CTCAE v5 | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE v5 | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE v5 | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE v5 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE v5 | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Thrush | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Vaginal infection | Infections and infestations | CTCAE v5 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE v5 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | CTCAE v5 | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE v5 | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE v5 | Systematic Assessment |
|
| Hyperphosphatemia | Metabolism and nutrition disorders | CTCAE v5 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Muscle cramp | Musculoskeletal and connective tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE v5 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE v5 | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE v5 | Systematic Assessment |
|
| Tremor | Nervous system disorders | CTCAE v5 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE v5 | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE v5 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v5 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE v5 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE v5 | Systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE v5 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D001982 |
| Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
| D005112 |
| Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |
|
| > 0.25mg/kg/d prednisone use |
|
|
| Lack of response |
|
| No involvement/Not evaluable |
|
| Eyes |
|
| Skin |
|
| Esophagus |
|
| Upper GI |
|
| Lower GI |
|
| Liver |
|
| Lungs |
|
| Joints and facia |
|
| Lack of Response |
|
| No involvement/Not evaluable |
|
| Eyes |
|
| Skin |
|
| Esophagus |
|
| Upper GI |
|
| Lower GI |
|
| Liver |
|
| Lungs |
|
| Joints and facia |
|
|
|