A Study to Evaluate Steroid-free Treatment for Standard-Risk aGVHD (BMT CTN 1501)
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|ClinicalTrials.gov Identifier: NCT02806947|
Recruitment Status : Active, not recruiting
First Posted : June 21, 2016
Last Update Posted : March 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute GVHD||Drug: Sirolimus Drug: Prednisone||Phase 2|
The study is a Phase II randomized, open label, multicenter trial designed to identify whether sirolimus is a potential alternative to prednisone as an up-front treatment for patients with standard-risk acute GVHD defined according to clinical and biomarker-based risk stratification.
Patients with previously untreated, standard-risk acute GVHD, according to the refined Minnesota Criteria, who are in need of systemic therapy, will have a 5 mL blood sample collected prior to randomization to assess their biomarker Ann Arbor Risk status. Ann Arbor scoring results will be provided 48-72 hours after randomization. Patients will begin their study treatment assignments within 24 hours of randomization. Those with biomarker results of combined AA1/2 risk will continue on their randomized study treatment and will be included for primary endpoint analysis (Day 28 complete or partial response) and all planned study procedures and assessments. In contrast, patients with AA3 biomarker risk and those patients with missing biomarker results may continue on their randomized therapies or start another therapy at their physicians' discretion. In addition, AA3 risk patients and those with missing results will not be considered in primary endpoint analysis, but will be included in a subset analysis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Phase II, Multicenter, Open Label, Study Evaluating Sirolimus and Prednisone in Patients With Refined Minnesota Standard Risk, Ann Arbor 1/2 Confirmed Acute Graft-Versus-Host Disease (BMT CTN #1501)|
|Actual Study Start Date :||October 2016|
|Estimated Primary Completion Date :||February 2019|
|Estimated Study Completion Date :||February 2020|
Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established.
Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
Active Comparator: Prednisone
Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established.
Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.
- Complete Response (CR) or Partial Response (PR) [ Time Frame: Day 28 ]Scoring of CR/PR is in comparison to the participant's acute GVHD status (score) on the day of randomization. CR is defined as a score of 0 for the GVHD grading in all evaluable organs. Partial response (PR) is defined as improvement in one or more organs involved with GVHD symptoms without progression in others.
- CR/PR and Steroid Dose less than 0.25 mg/kg per day [ Time Frame: Day 28 ]The proportion of patients with an acute GVHD response on Day 28 (CR or PR) and on a prednisone (or prednisone dose-equivalent corticosteroid) dose of 0.25 mg/kg per day or less.
- Proportion of Response [ Time Frame: Days 14, 28 and 56 ]Proportions of CR, PR, Mixed Response (MR), No Response (NR) and progression among surviving patients. MR is defined as improvement in one or more organs with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. No response is defined as absence of any improvement or progression.
- Treatment Failure [ Time Frame: Days 14, 28, and 56 ]Treatment failure is defined as either death, no response, progression, or administration of additional therapy beyond primary therapy for GVHD.
- Incidence of Chronic GVHD [ Time Frame: 6 and 12 Months ]Chronic GVHD is defined per NIH Consensus Criteria. The incidence of chronic GVHD will be computed for each treatment arm, including organ involvement and severity, and overall global composite score (mild/moderate/severe).
- Incidence of Systemic Infections [ Time Frame: 6 Months ]All microbiologically documented infections or significant infections requiring antibiotic/antifungal therapy occurring after initiation of therapy will be reported by site of disease, date of onset, and severity.
- Disease-Free Survival (DFS) [ Time Frame: 6 and 12 Months ]The events for DFS are death and relapse of the underlying malignancy.
- Non-Relapse Mortality [ Time Frame: 6 and 12 Months ]The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy. Cumulative incidence of non-relapse mortality will be estimated (treating relapse as a competing risk) and curves will be compared using Gray's test.
- GVHD-free Survival [ Time Frame: 6 and 12 Months ]Both acute and chronic GVHD will be considered in this estimate.
- Event Free Survival [ Time Frame: 6 and 12 Months ]Event-free survival is defined as freedom from acute GVHD progression, chronic GVHD, malignancy relapse and mortality.
- Overall Survival (OS) [ Time Frame: 6 and 12 Months ]OS is defined as alive at study endpoint
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): NCT02806947
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|Study Director:||Mary Horowitz, MD, MS||Center for International Blood and Marrow Transplant Research|