RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Haploidentical Related, Partially HLA-Mismatched, or Matched Unrelated Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia

Quick Facts

Study Start:2025-05-31

Study Completion:2029-02-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06517641

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age 3 years to 75 years 2. Confirmed diagnosis of acquired SAA defined as: 3. 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. 4. Available donor as defined in the protocol. 5. Participant and/or legal guardian must sign informed consent. 6. Adequate organ function defined by institutional transplant standards or defined as below: 1. 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. 2. Hepatic: Total bilirubin \< 2.0 mg/dL unless Gilbert's disease is present 3. 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. 4. Pulmonary: 7. Karnofsky or Lansky performance status ≥ 60%. 8. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.	1. 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. 2. 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). 3. Formal diagnosis of MDS by World Health Organization (WHO) 2022 or International Consensus Classification (ICC). 4. 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. 5. 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. 6. 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. 7. Prior allogeneic stem cell transplant. 8. Prior solid organ transplant. 9. 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. 10. 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. 11. Female participants who are pregnant, as detected using a pregnancy test as per institutional practice, or breast-feeding. 12. 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. * Prior infections must be controlled * HepB participants are eligible if on effective suppressive therapy and otherwise meet inclusion/exclusion criteria * HepC participants are eligible if otherwise meet inclusion/exclusion criteria

Inclusion Criteria

Exclusion Criteria

1. Age 3 years to 75 years
2. Confirmed diagnosis of acquired SAA defined as:
3. 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.
4. Available donor as defined in the protocol.
5. Participant and/or legal guardian must sign informed consent.
6. Adequate organ function defined by institutional transplant standards or defined as below:
1. 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.
2. Hepatic: Total bilirubin \< 2.0 mg/dL unless Gilbert's disease is present
3. 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.
4. Pulmonary:
7. Karnofsky or Lansky performance status ≥ 60%.
8. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.

1. 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.
2. 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).
3. Formal diagnosis of MDS by World Health Organization (WHO) 2022 or International Consensus Classification (ICC).
4. 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.
5. 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.
6. 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.
7. Prior allogeneic stem cell transplant.
8. Prior solid organ transplant.
9. 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.
10. 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.
11. Female participants who are pregnant, as detected using a pregnancy test as per institutional practice, or breast-feeding.
12. 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.
* Prior infections must be controlled
* HepB participants are eligible if on effective suppressive therapy and otherwise meet inclusion/exclusion criteria
* HepC participants are eligible if otherwise meet inclusion/exclusion criteria

Contacts and Locations

Study Contact

Jennifer Romeril

CONTACT

301-251-1161

bmtctn2207@emmes.com

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

United States

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

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Emory Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Blood and Marrow Transplant Center at Northside Hospital

Atlanta, Georgia, 30342

United States

University of Kansas Medical Center

Westwood, Kansas, 66205

United States

Johns Hopkins University

Baltimore, Maryland, 21218

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

United States

Levine Cancer Institute

Charlotte, North Carolina, 28204

United States

Duke University Health System

Durham, North Carolina, 27705

United States

The Ohio State University

Columbus, Ohio, 43210

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

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Medical College of Wisconsin

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-05-31

Study Completion Date2029-02-01

Study Record Updates

Study Start Date2025-05-31

Study Completion Date2029-02-01

Terms related to this study

Additional Relevant MeSH Terms

Severe Aplastic Anemia