Clinical Trial of Upfront Haploidentical or Unrelated Donor BMT to Restore Normal Hematopoiesis in Aplastic Anemia

NCT06517641 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: BMT CTN 2207BMT CTN Protocol 2207
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 25

Brief Summary

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

Conditions

Severe Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Percentage of Participants with Overall survival (OS) at One year post conditioning

  1 year after initiation of conditioning

• Percentage of Participants with Failure-Free Survival (FFS) at One year post conditioning

  1 year after initiation of conditioning

• Participants Alive and Engrafted at One year post conditioning

  1 year after initiation of conditioning

• Percentage of Participants with Neutrophil Recovery post-transplant

  Day 28 and Day 56 post-HSCT

• Percentage of Participants with Red Blood Cell Recovery post-transplant

  Day 100, Day 180, and Day 365 post-HSCT

Study Arms (2)

Haploidentical transplantation

ACTIVE COMPARATOR

Patients receiving bone marrow transplanted from a haploidentical related donor will be included in this arm.

Drug: Haploidentical donor bone marrow transplant

Unrelated donor transplantation

ACTIVE COMPARATOR

Patients receiving bone marrow transplanted from an unrelated donor will be included in this arm.

Drug: Unrelated donor bone marrow transplant

Interventions

Haploidentical donor bone marrow transplant DRUG

Drugs: 1. Antithymocyte Globulin (ATG) dose 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. 2. Fludarabine dose will be 30 mg/m\^2 IV daily for 5 days from Day -6 to Day -2. 3. 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. 4. Tacrolimus should be started on Day +5 and administered to maintain a level of 10-15 ng/mL. 5. Mycophenolate mofetil (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 through Day +35. 6. G-CSF will be given IV or SQ starting on Day +5 at 5 mcg/kg/day until ANC is \> 1500 for 3 days. Radiation: 1\. Total Body Irradiation (TBI): will be given as a single dose of 400 cGy on Day -1. Procedure: 1\. HSCT: Eligible patients will receive a haploidentical donor bone marrow transplant.

Haploidentical transplantation

Unrelated donor bone marrow transplant DRUG

Drugs: 1. Antithymocyte Globulin (ATG) dose 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. 2. Fludarabine dose will be 30 mg/m\^2 IV daily for 5 days from Day -6 to Day -2. 3. 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. 4. Tacrolimus should be started on Day +5 and administered to maintain a level of 10-15 ng/mL. 5. Mycophenolate mofetil (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 through Day +35. 6. G-CSF will be given IV or SQ starting on Day +5 at 5 mcg/kg/day until ANC is \> 1500 for 3 days. Radiation: 1\. Total Body Irradiation (TBI): will be given as a single dose of 400 cGy on Day -1. Procedure: 1\. HSCT: Eligible patients will receive an unrelated donor bone marrow transplant.

Unrelated donor transplantation

Eligibility Criteria

• Age: 3 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 3 years to 75 years
• Confirmed diagnosis of acquired SAA defined as:
• a. Bone marrow cellularity \< 25% or variable marrow cellularity but with \< 30% residual hematopoietic cells deemed HYPOcellular for age AND b. Two (2) out of 3 of the following (in peripheral blood). i. Neutrophils \< 0.5 x109/L ii. Platelets \< 20 x109/L iii. Reticulocyte count \< 20 x109/L (\< 60 x 109/L using an automated analysis)
• No suitable fully matched related donor as per Investigator's discretion (6/6 match for HLA A and B at intermediate or high-resolution and DRB1 at high-resolution using deoxyribonucleic acid \[DNA\]-based typing) available.
• Available donor as defined in the protocol.
• Participant and/or legal guardian must sign informed consent.
• Adequate organ function defined by institutional transplant standards or defined as below:
• Cardiac: Left ventricular ejection fraction (LVEF) at rest \> 40% with no clinical signs of cardiac failure. For participants aged \< 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or multigated acquisition (MUGA) may be substituted for LVEF.
• Hepatic: Total bilirubin \< 2.0 mg/dL unless Gilbert's disease is present
• Renal: For participants \> 13.0 years of age at the time of enrollment: estimated creatinine clearance (CrCl) \> 60 mL/minute (per institutional standard). For participants \< 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 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m2.
• Pulmonary:
• i. For participants \> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO, corrected/adjusted for hemoglobin \[Hb\]) \> 50%, or Spirometry with forced expiratory volume 1 (FEV1) \> 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) \> 50% predicted.
• ii. For participants \< 13.0 years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care \[e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%\]).
• Karnofsky or Lansky performance status ≥ 60%.
• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.

You may not qualify if:

• Inherited bone marrow failure syndromes such as Fanconi anemia and short telomere syndromes must be ruled out according to center standards. It is recommended that functional testing for Fanconi Anemia (di-epoxybutane \[DEB\] chromosomal breakage analysis) and telomere length assessment be performed. If available, genetic panels for inherited bone marrow failure syndromes can be considered as an alternative to functional testing.
• Clonal cytogenetic abnormalities consistent with pre-MDS or MDS on marrow examination (e.g., monosomy 7 and other MDS-defining changes per recent pathology guidelines).
• Formal diagnosis of MDS by World Health Organization (WHO) 2022 or International Consensus Classification (ICC).
• Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, -DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and immediately prior to initiation of recipient preparative regimen to ensure there is confirmation of no DSA to the selected donor when conditioning starts.
• Prior desensitization attempt for HLA antibodies to chosen donor. Any intervention with the sole intent to reduce the level of HLA DSA, (e.g., plasmapheresis, intravenous immunoglobulin \[IVIG\], MMF, etc.) would constitute a desensitization attempt.
• Prior treatment for SAA (e.g., immunosuppressive therapy using ATG, calcineurin inhibitors \[CNIs\], thrombopoietin receptor agonists or androgens). Short courses of steroids or IVIG that were not explicitly administered for SAA therapy will be allowed.
• Prior allogeneic stem cell transplant.
• Prior solid organ transplant.
• Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® (Sanofi) that would prohibit use for the participant as this study requires use of the Thymoglobulin® (Sanofi) 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.
• Female participants who are pregnant, as detected using a pregnancy test as 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.
• Of note, participants with seropositivity for the human immunodeficiency virus (HIV) may be considered if viral load is undetectable. Similarly, carriers of hepatitis B (HepB) or hepatitis C (HepC) may not have a detectable viral load of HepB virus or HepC virus.
• Participants with HIV that is well-controlled on combination antiretroviral therapy and no AIDS related complications within the past 12 months are eligible.
• Infections other than HIV:

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Sanofi: collaborator

Study Sites (25)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Blood and Marrow Transplant Center at Northside Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21218, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine, Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University Health System

Durham, North Carolina, 27705, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37235, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Links

• Blood and Marrow Transplant Clinical Trials Network Website

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Central Study Contacts

Jennifer Romeril

CONTACT

301-251-1161; bmtctn2207@emmes.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a parallel cohort study comprised of two cohorts - patients receiving haploidentical donor transplant and patients receiving unrelated donor transplant. The goal is 60 participants in total who initiate the protocol-specified conditioning regimen, 30 in each of the haploidentical and unrelated donor transplant cohorts. Additional participants may be screened, consented, and registered in order to reach accrual goals.

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 24, 2024
• Study Start: May 12, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Within 6 months of official study closure at participating sites
• Access Criteria: Available to public

Locations

US (25)