A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-vs-Host Disease (BMT CTN 2002) (2002)
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|ClinicalTrials.gov Identifier: NCT04934670|
Recruitment Status : Recruiting
First Posted : June 22, 2021
Last Update Posted : August 2, 2022
|Condition or disease||Intervention/treatment||Phase|
|Steroid-Refractory Acute Graft Versus Host Disease||Drug: T-Guard Drug: Ruxolitinib||Phase 3|
Graft-vs-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) patients; it occurs when the new cells from a transplant attack the recipient's body. Acute GVHD (aGVHD) typically develops within the first three months after HSCT and is typically treated with steroid therapy. A significant fraction of the aGVHD population (10-50%) fail to respond to treatment and are deemed steroid-refractory (SR).
Participants that develop Grade III or IV SR aGVHD will be randomized to receive T-Guard or ruxolitinib and will be followed for approximately 180 days. Participants will be stratified by center region (US vs. Europe) and age group (at least 55 years vs. under 55). Participants randomized to the T-Guard arm will receive 4 doses administered intravenously as four 4-hour infusions, and participants randomized to the ruxolitinib arm will receive one dose administered orally twice a day. The primary analysis will include all participants that are randomized.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||246 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Participants will be randomized at a ratio of 1:1 between the treatment arms|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Randomized, Open-Label, Multicenter Study, to Compare T-Guard to Ruxolitinib for the Treatment of Patients With Grade III or IV Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) (BMT CTN 2002)|
|Actual Study Start Date :||June 16, 2022|
|Estimated Primary Completion Date :||June 1, 2025|
|Estimated Study Completion Date :||June 1, 2026|
Participants will be administered four doses of T-Guard intravenously for a 4-hour period every other day
T-Guard will be administered intravenously inpatient over 4 hours every 2 calendar days on Days 0, 2, 4, and 6, at a dose of 4mg/m2 Body Surface Area (BSA).
Active Comparator: Ruxolitinib
Participants will take ruxolitinib twice daily for continuous daily dosing
Ruxolitinib will be administered orally twice a day starting on Day 0 through Day 56, at a dose of 10mg. Ruxolitinib taper can be initiated starting on Day 56 for participants responding to treatment, tapering will be done according to institutional practices.
- Complete Response (CR) [ Time Frame: Day 28 ]The primary objective of this trial is to assess the rate of CR on Day 28 post-randomization in Grades III and IV SR-aGVHD patients treated with T-Guard treatment in comparison to ruxolitinib.
- Overall Survival (OS) [ Time Frame: Days 60, 90, and 180 ]OS is defined as survival of death from any cause. The time from randomization until death from any cause will be described for each arm.
- Duration of Complete Response (DoCR) [ Time Frame: Day 28 ]DoCR will be evaluated only in the set of participants who are in CR at Day 28 post-randomization. The primary definition of DoCR is the time from Day 28 until an aGVHD target organ worsens by at least 1 stage and requires a significant escalation in treatment, or death.
- Time to Complete Response (CR) [ Time Frame: Days 28 and 56 ]The time from randomization until first attaining a CR will be described for each treatment arm, with death and additional systemic treatment for aGVHD treated as competing risks.
- Overall Response Rate (ORR) [ Time Frame: Days 14, 28, and 56 ]Overall response is defined as either a complete or partial response (CR+PR). The ORR will be estimated for each treatment arm.
- Proportion of Response [ Time Frame: Days 6, 14, 28, and 56 ]The proportion of participants in each aGVHD response category will be described for each treatment arm.
- Non-relapse Mortality (NRM) [ Time Frame: Days 90 and 180 ]NRM is defined as death from any cause other than malignancy relapse/progression. The time from randomization until NRM will be described for each treatment arm.
- Relapse-free Survival (RFS) [ Time Frame: Day 180 ]RFS is defined as being alive and free of malignancy relapse/progression. The time from randomization until malignancy relapse/progression or death will be described for each arm.
- GVHD-free Survival [ Time Frame: Days 90 and 180 ]GVHD-free survival is defined as being alive, in CR, and free of cGVHD. The proportion of participants with GVHD-free survival post-randomization will be estimated for each treatment arm.
- Chronic GVHD (cGVHD) [ Time Frame: Day 180 ]The maximum severity of cGVHD post-randomization will be tabulated by arm. The time from randomization until onset of cGVHD of any severity (mild, moderate, or severe) will be described for each treatment arm.
- Relapse/Progression of Underlying Malignancy [ Time Frame: Day 180 ]The time from randomization until malignancy relapse/progression will be described for each treatment arm, with death prior to relapse/progression treated as a competing risk.
- Incidence of Infections [ Time Frame: Day 90 ]The frequency of Grade 2-3 infections occurring after randomization will be tabulated by infection site, date of onset, and severity. The cumulative incidence of Grade 2-3 infections will be described by treatment arm.
- Incidence of Toxicities [ Time Frame: Day 56 ]The frequency of Grade 3-5 toxicities per CTCAE version 5 occurring after randomization will be tabulated by organ system for each treatment arm. The maximum severity of reported toxicities during that period will also be summarized.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04934670
|Contact: Heather Wittsackfirstname.lastname@example.org|
|Contact: Adam Mendizabal, PhDemail@example.com|
|Study Director:||Mary Horowitz, MD, MS||Center for International Blood and Marrow Transplant Research|
|Study Director:||Willem Klaasen||Xenikos, BV|