Optimizing Haploidentical Aplastic Anemia Transplantation (BMT CTN 1502)
CHAMP
3 other identifiers
interventional
32
1 country
28
Brief Summary
This study is a prospective, multicenter phase II study with patients receiving haploidentical transplantation for Severe Aplastic Anemia (SAA). The primary objective is to assess overall survival (OS) at 1 year post-hematopoietic stem cell transplantation (HSCT).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2017
Typical duration for phase_2
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 27, 2016
CompletedFirst Posted
Study publicly available on registry
September 28, 2016
CompletedStudy Start
First participant enrolled
July 3, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 17, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 17, 2021
CompletedResults Posted
Study results publicly available
July 12, 2022
CompletedMarch 31, 2026
March 1, 2026
4.1 years
September 27, 2016
April 29, 2022
March 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Overall Survival (OS)
Overall survival (OS) is the primary endpoint of this study. The time to this event is the time from transplant to death from any cause or last follow-up or 1 year from transplant, whichever occurs first. The one-year OS probability and its 95% confidence interval were estimated using the Kaplan-Meier estimator and Greenwood's formula.
1 year
Secondary Outcomes (19)
Percentage of Participants With Neutrophil Recovery
Day 28 and 56
Percentage of Participants With Platelet Recovery
Day 100
Participants Alive With Sustained Engraftment
1 year
Percentage of Participants With Graft-Failure-Free Survival
1 year
Percentage of Participants With Primary Graft Failure
Day 56
- +14 more secondary outcomes
Study Arms (1)
Haplo Bone Marrow HSCT
EXPERIMENTALPatients will be treated with a preparative regimen of Antithymocyte Globulin (ATG) (4.5 mg/kg), fludarabine (150 mg/m\^2), cyclophosphamide (29 mg/kg), and low dose total body irradiation (TBI) (200 cGy) before undergoing the haplo HSCT. GVHD prophylaxis will be with post-HSCT cyclophosphamide (100 mg/kg), tacrolimus, and mycophenolate mofetil (MMF). G-CSF will be administered post-transplant.
Interventions
Administration of ATG will be 0.5 mg/kg IV on Day -9 over 6 hours and 2 mg/kg IV on Days -8 and -7 over 4 hours.
Cyclophosphamide dose will be 14.5 mg/kg IV daily for 2 days (Day -6 to Day -5) prior to transplantation and 50 mg/kg IV daily for 2 days (Day +3 to Day +4) after transplantation.
TBI is to be delivered in a single dose of 200 cGy on Day -1.
Eligible patients without a fully matched related or unrelated donor available will undergo haploidentical bone marrow transplant.
Tacrolimus should be started on Day +5 and administered to maintain a level of 10-15 ng/mL.
MMF dose will be 15 mg/kg PO three times a day (TID) up to 1 gm TID (or IV equivalent) starting on Day +5.
G-CSF will be given IV or SQ starting on Day +5 at 5 mcg/kg/day until ANC is \> 1500 for 3 days.
Fludarabine dose will be 30 mg/m\^2 IV daily for 5 days from Day -6 to Day -2.
Eligibility Criteria
You may qualify if:
- Patient is \< 75 years of age at time of enrollment.
- Confirmed diagnosis of SAA, either from initial diagnosis or follow-up assessments, defined as:
- Bone marrow cellularity \< 25% or marrow cellularity \< 50% but with \< 30% residual hematopoietic cells.
- Two out of three of the following (in peripheral blood): Neutrophils \< 0.5 x10\^9/L, Platelets \< 20 x10\^9/L, or Reticulocyte count \< 20 x10\^9/L (\<60 x 10\^9/L using an automated analysis)
- No suitable fully matched related sibling donor (6/6 match for human leukocyte antigen (HLA)-A and B at intermediate or high resolution and DRB1 at high resolution using DNA-based typing) available.
- Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA.
- Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc. Eligible haploidentical donors will have 2-4 mismatches if HLA-A, -B, -C, and -DRB1 typing is used; 2-5 mismatches if HLA-A, -B, -C, -DRB1, and -DQB1 typing is used; and 2-6 mismatches if HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 typing is used. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must demonstrate that they are a full haplotype match by being identical at a minimum of one allele (at high resolution DNA-based typing) at the following genetic loci: HLA-A, -B, -C, and DRB1 if 8 allele typing is used; HLA-A, -B, -C, -DRB1, and -DQB1 if 10 allele typing is used; and HLA-A, -B, -C, -DRB1-, DQB1, and -DPB1 is 12 allele typing is used by the local center. See Section 2.4 for additional information.
- Patient and/or legal guardian must sign informed consent for HSCT.
- The haplo donor and/or legal guardian must be able to sign informed consent documents.
- The potential haplo donor must be willing and able to donate bone marrow.
- The weight of the haplo donor must be ≥ 20 kg.
- Adequate organ function defined as:
- Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40%. For patients aged \< 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or Multi Gated Acquisition Scan (MUGA) may be substituted for LVEF.
- Hepatic: Total bilirubin \< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5.0 x ULN for age.
- Renal: For patients \> 13.0 years of age at the time of enrollment: estimated creatinine clearance \> 50 mL/minute (using the Cockcroft-Gault formula and actual body weight). For patients \< 13.0 years of age at enrollment: Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m\^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m\^2.
- +3 more criteria
You may not qualify if:
- Inherited bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center standard.
- Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
- Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) \> 1000 by solid phase immunoassay).
- Prior allogeneic stem cell transplant.
- Prior solid organ transplant.
- Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® that would prohibit use for the patient as this study requires use of the Thymoglobulin® preparation of ATG.
- Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment.
- Seropositive for the human immunodeficiency virus (HIV).
- Active Hepatitis B or C determined by a detectable viral load of HBV or HCV.
- Female patients who are pregnant (per institutional practice) or breast-feeding.
- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent \> 5 years previously will be allowed. Cancer treated with curative intent ≤ 5 years previously will not be allowed unless approved by the Protocol Chairs and/or Protocol Officer.
- Alemtuzumab or ATG within 2 weeks of enrollment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical College of Wisconsinlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Marrow Donor Programcollaborator
Study Sites (28)
City of Hope National Medical Center
Duarte, California, 91010, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital and Research Center Oakland
Oakland, California, 94618, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
Miami Children's Hospital
Miami, Florida, 33155, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33624, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Indiana University Medical Center/ Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Louisville/Kosair Children's Hospital
Louisville, Kentucky, 40202, United States
Johns Hopkins Unversity
Baltimore, Maryland, 21231, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48105, United States
Karmanos Cancer Institute/Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Children's Mercy Hospital and Clinics
Kansas City, Missouri, 64108, United States
Washington University/Barnes Jewish Hospital
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Oregon Health and Science University
Portland, Oregon, 97239-3098, United States
Penn State College of Medicine/The Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Transplant Institute
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Children's Hospital of Wisconsin/Midwest Children's Cancer
Milwaukee, Wisconsin, 53211, United States
Related Publications (1)
DeZern AE, Eapen M, Wu J, Talano JA, Solh M, Davila Saldana BJ, Karanes C, Horwitz ME, Mallhi K, Arai S, Farhadfar N, Hexner E, Westervelt P, Antin JH, Deeg HJ, Leifer E, Brodsky RA, Logan BR, Horowitz MM, Jones RJ, Pulsipher MA. Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2022 Sep;9(9):e660-e669. doi: 10.1016/S2352-3026(22)00206-X. Epub 2022 Jul 27.
PMID: 35907408RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Company
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD, MS
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 27, 2016
First Posted
September 28, 2016
Study Start
July 3, 2017
Primary Completion
August 17, 2021
Study Completion
August 17, 2021
Last Updated
March 31, 2026
Results First Posted
July 12, 2022
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).