Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

NCT ID: NCT02845596

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2023-07-19

Brief Summary

The purpose of this study is to determine the feasibility of comparing outcomes of patients treated de novo with immunosuppressive therapy (IST) versus matched unrelated donor (MUD) hematopoietic stem cell transplant (HSCT) for pediatric acquired severe aplastic anemia.

Detailed Description

A major challenge in treating pediatric Severe Aplastic Anemia (SAA) is the determination of best primary therapy for patients who lack a fully matched related donor for HSCT. Good survival outcomes have been seen with IST, but initial and late failures, CSA dependence, persistent cytopenias and secondary Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) in a portion of patients leave considerable room for improvement. MUD HSCT survival in SAA has markedly improved, but a direct comparison of this approach with IST is necessary to determine whether this approach is feasible and will lead to better Event Free Survival. This trial will address the feasibility of randomization, test whether patients can be evaluated in a timely fashion and safely begin therapy with MUD HSCT or IST, and give a preliminary assessment of the safety of up-front MUD HSCT. If successful, this trial will lead to a future prospective trial comparing directly IST to MUD HSCT in this disease.

Conditions

Severe Aplastic Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Immunosuppressive Therapy

Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.

Group Type: ACTIVE_COMPARATOR

cyclosporine

Intervention Type: DRUG

cyclosporine

horse anti-thymocyte globulin (ATG)

Intervention Type: DRUG

horse anti-thymocyte globulin (ATG)

Immunosuppressive Therapy (IST)

Intervention Type: PROCEDURE

Immunosuppressive Therapy (IST)

Matched Unrelated Stem Cell Transplant

Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.

Group Type: ACTIVE_COMPARATOR

cyclosporine

Intervention Type: DRUG

cyclosporine

Matched Unrelated Donor Hematopoietic Stem Cell Transplant

Intervention Type: PROCEDURE

Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)

rabbit anti-thymocyte globulin (ATG)

Intervention Type: DRUG

rabbit anti-thymocyte globulin (ATG)

methotrexate

Intervention Type: DRUG

methotrexate

fludarabine

Intervention Type: DRUG

fludarabine

cyclophosphamide

Intervention Type: DRUG

cyclophosphamide

low-dose total body irradiation (TBI)

Intervention Type: RADIATION

low-dose total body irradiation (TBI)

Interventions

cyclosporine

cyclosporine

Intervention Type: DRUG

Matched Unrelated Donor Hematopoietic Stem Cell Transplant

Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)

Intervention Type: PROCEDURE

horse anti-thymocyte globulin (ATG)

horse anti-thymocyte globulin (ATG)

Intervention Type: DRUG

rabbit anti-thymocyte globulin (ATG)

rabbit anti-thymocyte globulin (ATG)

Intervention Type: DRUG

methotrexate

methotrexate

Intervention Type: DRUG

fludarabine

fludarabine

Intervention Type: DRUG

cyclophosphamide

cyclophosphamide

Intervention Type: DRUG

low-dose total body irradiation (TBI)

low-dose total body irradiation (TBI)

Intervention Type: RADIATION

Immunosuppressive Therapy (IST)

Immunosuppressive Therapy (IST)

Intervention Type: PROCEDURE

Other Intervention Names

ATGAM; Thymoglobulin

Eligibility Criteria

Inclusion Criteria

1. Confirmed diagnosis of idiopathic SAA, defined as:

• Bone marrow cellularity <25%, or <30% hematopoietic cells.
• Two out of three of the following (in peripheral blood): neutrophils <0.5 x109/L, platelets <20 x109/L, reticulocyte count <60 x109/L with hemoglobin <8g/dL.

2. Age ≤25 years old.

3. No suitable fully matched related donor available (minimum 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).

4. At least two unrelated donors noted on National Marrow Donor Program (NMDP) search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).

5. Signed informed consent for the randomized trial by patient and/or legal guardian.

Exclusion Criteria

1. Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis congenita, but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman Diamond syndrome, this syndrome must be excluded by pancreatic isoamylase testing or gene mutation analysis. Note: pancreatic isoamylase testing is not accurate in children less than 3 years.

2. Clonal cytogenetic abnormalities or fluorescence In Situ Hybridization (FISH) pattern consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (see section 4.2.3.1 for details of the required MDS FISH panel).

3. Known severe allergy to horse ATG.

4. Prior allogeneic stem cell transplant.

5. Prior solid organ transplant.

6. Infection with human immunodeficiency virus (HIV).

7. Active Hepatitis B or C. This should be excluded in patients where there is clinical suspicion of hepatitis (e.g. elevated LFTs).

8. Female patients who are pregnant or breast-feeding.

9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael Pulsipher

OTHER

Sponsor Role: lead

Responsible Party

Michael Pulsipher

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Pulsipher, MD

Role: STUDY_CHAIR

Children's Hospital Los Angeles

David A Williams, MD

Role: STUDY_CHAIR

Boston's Childrens Hospital

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Stanford Lucile Packard Children's Hospital

Palo Alto, California, United States

UCSF

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Cohen Children's Medical Center

Queens, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

TransIT NMD 1601

Identifier Type: -

Identifier Source: org_study_id