Clinical Trial of Upfront Haploidentical or Unrelated Donor BMT to Restore Normal Hematopoiesis in Aplastic Anemia
NCT Number: NCT06517641
Acronym: BMT CTN CureAA
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Severe Aplastic Anemia
Interventions: DRUG: Haploidentical donor bone marrow transplant|DRUG: Unrelated donor bone marrow transplant
Sponsor: Medical College of Wisconsin
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)|National Cancer Institute (NCI)|Sanofi
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2029-02-01
Locations: City of Hope, Duarte, California, 91010, United States|University of California, Los Angeles, Los Angeles, California, 90095, United States|Stanford University, Stanford, California, 94305, United States|Johns Hopkins University, Baltimore, Maryland, 21218, United States|Mayo Clinic, Rochester, Minnesota, 55905, United States|Levine Cancer Institute, Charlotte, North Carolina, 28204, United States|University of Oklahoma, Oklahoma City, Oklahoma, 73117, United States|University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States|Vanderbilt University, Nashville, Tennessee, 37235, United States|Huntsman Cancer Institute, Salt Lake City, Utah, 84112, United States

Summary:
BMT CTN 2207 will investigate the use of marrow transplantation for treatment of severe aplastic anemia that has not previously been treated.

Primary Outcome Measures: Graft versus host disease (GVHD)-free failure-free survival (GFFS) at One year, The primary endpoint is GFFS at 1 year after initiation of conditioning. Events for GFFS include Grade III-IV aGVHD, cGVHD requiring immunosuppression, primary or secondary graft failure requiring second definitive therapy, failure to receive an HSCT infusion, and death. GFFS is defined as the time interval from start of conditioning until the first of these events occurs. For failure to receive an HSCT infusion, the date will be at the time the decision not to proceed to HSCT is made., 1 year after initiation of conditioning
Secondary Outcome Measures: Percentage of Participants with Overall survival (OS) at One year post conditioning, Events for OS include death from any cause. OS is defined as the time interval from initiation of conditioning until death. The OS probability will be assessed at 1 year after initiation of conditioning., 1 year after initiation of conditioning|Percentage of Participants with Failure-Free Survival (FFS) at One year post conditioning, Events for FFS include treatment failure or death. Treatment failure is defined as the initiation of treatment with a second definitive therapy. FFS is defined as the time interval from start of conditioning until the start date of a second definitive therapy or death, whichever occurs first., 1 year after initiation of conditioning|Participants Alive and Engrafted at One year post conditioning, The proportion of patients who are alive with donor cells present at 1 year after initiation of conditioning will be described, where the presence of donor cells is defined as achieving at least 5% myeloid donor chimerism (whole blood or marrow) in the most recent measurement through 1 year., 1 year after initiation of conditioning|Percentage of Participants with Neutrophil Recovery post-transplant, Neutrophil recovery is achieving an ANC ≥ 0.5 x109/L for 3 consecutive measurements on different days, with the first of the 3 days being defined as the day of neutrophil recovery. The cumulative incidences of neutrophil recovery at Day +28 and Day +56 post-HSCT will be estimated., Day 28 and Day 56 post-HSCT|Percentage of Participants with Red Blood Cell Recovery post-transplant, Red blood cell (RBC) recovery is defined as Hb level ≥ 7 g/dL with no red cell transfusion in the preceding 7 days. The first day of the 7 days will be defined as the day of RBC recovery. The cumulative incidences of RBC recovery at Day +100, Day +180, and Day +365 post-HSCT will be estimated., Day 100, Day 180, and Day 365 post-HSCT|Percentage of Participants with Platelet Recovery post-transplant, Platelet recovery is defined by achieving a platelet count ≥ 20 x 109/L with no platelet transfusions in the preceding 7 days. The first 7 days of the sustained platelet count will be defined as the day of platelet recovery. The cumulative incidence of platelet recovery at Day +100 post-HSCT will be estimated., Day 100 post-HSCT|Percentage of Participants with Primary Graft Failure post-transplant, * Primary Graft Failure is defined as the occurrence of any of the following:

  1. Lack of neutrophil recovery by Day +56 post-HSCT.
  2. Failure to achieve at least 5% myeloid donor chimerism any measurement up to and including Day +56 post-HSCT.
  3. Administration of a second definitive therapy, which is defined as a second transplant or a course of ATG.
* The proportion of patients with primary graft failure through Day +56 post-HSCT will be estimated., Day 56 post-HSCT|Percentage of Participants with Secondary Graft Failure post-transplant, * Secondary Graft Failure is defined as the occurrence of any of the following:

  1. Initial neutrophil recovery with donor chimerism greater than or equal to 5%, followed by sustained subsequent decline in ANC with donor chimerism declining to less than 5%.
  2. Administration of a second definitive therapy, which is defined as a second transplant or a course of ATG.
* The cumulative incidence of secondary graft failure at 1 year post-HSCT will be estimated., 1 year post-HSCT|Percentage of Participants with any Graft Failure (primary or secondary) post-transplant, The time from transplant until any graft failure (primary or secondary) will be described for each transplant cohort using the Aalen-Johansen estimator, with death treated as a competing risk. Estimates and 90% CIs of the cumulative incidence of any graft failure will be provided at Day +365 post-HSCT for each cohort., 1 year post-HSCT|Participants with Hematologic Response post-transplant, Hematologic response will be assessed according to the modified NIH criteria determined at Day +100, Day +180, and Day +365 post-HSCT. Complete response (CR) is defined as meeting all 3 peripheral blood count criteria: 1) ANC \> 1x 109/L; 2) Hb \> 10g/dL; and 3) platelet count \> 100 x 109/L. Partial response (PR) is defined as blood counts no longer satisfying criteria for SAA and having transfusion independence (defined as no need for packed red blood cell \[PRBC\] or platelet transfusions) but insufficient for a CR., Day 100, Day 180, and Day 365 post-HSCT|Percentage of participants with Grades II-IV and III-IV Acute GVHD at Day 100 post-transplant, Acute GVHD are graded according to the BMT CTN Technical Guideline. The cumulative incidences of Grade II-IV and Grade III-IV acute GVHD at Day +100 post-HSCT will be estimated., Day 100 post-HSCT|Percentage of participants with Chronic GVHD at One year post-transplant, Chronic GVHD are graded according to the BMT CTN Technical Guideline. The cumulative incidences of all chronic GVHD and of chronic GVHD requiring immunosuppression will be estimated., Day 365 post-HSCT