Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

NCT02845596 | Completed DMC

• 1 other identifier: TransIT NMD 1601
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

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.

Conditions

Severe Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Percentage of patients randomized to HSCT that actually complete HSCT

  Feasibility of comparing outcomes of patients treated de novo with IST versus matched unrelated donor HSCT for pediatric acquired severe aplastic anemia as defined by percentage of patients randomized to HSCT that actually complete HSCT.

  4 years

Secondary Outcomes (18)

• Time from screening consent to randomization

  4 years

• Number of patients that fail to receive their primary assigned therapy (HSCT or IST).

  4 years

• Reasons why patients fail to receive their primary assigned therapy (HSCT or IST).

  4 years

• Treatment-related mortality at one year from randomization in both arms

  1 Year

• Overall Survival at one year from randomization in both arms

  1 Year

Study Arms (2)

Immunosuppressive Therapy

ACTIVE COMPARATOR

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

Drug: cyclosporine; Drug: horse anti-thymocyte globulin (ATG); Procedure: Immunosuppressive Therapy (IST)

Matched Unrelated Stem Cell Transplant

ACTIVE COMPARATOR

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.

Drug: cyclosporine; Procedure: Matched Unrelated Donor Hematopoietic Stem Cell Transplant; Drug: rabbit anti-thymocyte globulin (ATG); Drug: methotrexate; Drug: fludarabine; Drug: cyclophosphamide; Radiation: low-dose total body irradiation (TBI)

Interventions

cyclosporine DRUG

cyclosporine

Immunosuppressive Therapy; Matched Unrelated Stem Cell Transplant

Matched Unrelated Donor Hematopoietic Stem Cell Transplant PROCEDURE

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

Matched Unrelated Stem Cell Transplant

horse anti-thymocyte globulin (ATG) DRUG

horse anti-thymocyte globulin (ATG)

Also known as: ATGAM

Immunosuppressive Therapy

rabbit anti-thymocyte globulin (ATG) DRUG

rabbit anti-thymocyte globulin (ATG)

Also known as: Thymoglobulin

Matched Unrelated Stem Cell Transplant

methotrexate DRUG

methotrexate

Matched Unrelated Stem Cell Transplant

fludarabine DRUG

fludarabine

Matched Unrelated Stem Cell Transplant

cyclophosphamide DRUG

cyclophosphamide

Matched Unrelated Stem Cell Transplant

low-dose total body irradiation (TBI) RADIATION

low-dose total body irradiation (TBI)

Matched Unrelated Stem Cell Transplant

Immunosuppressive Therapy (IST) PROCEDURE

Immunosuppressive Therapy (IST)

Immunosuppressive Therapy

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Age ≤25 years old.
• 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).
• 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).
• Signed informed consent for the randomized trial by patient and/or legal guardian.

You may not qualify if:

• 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.
• 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).
• Known severe allergy to horse ATG.
• Prior allogeneic stem cell transplant.
• Prior solid organ transplant.
• Infection with human immunodeficiency virus (HIV).
• Active Hepatitis B or C. This should be excluded in patients where there is clinical suspicion of hepatitis (e.g. elevated LFTs).
• Female patients who are pregnant or breast-feeding.
• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.

Sponsors & Collaborators

• Michael Pulsipher: lead

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

UCSF

San Francisco, California, 94123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cohen Children's Medical Center

Queens, New York, 11040, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Cyclosporine; Antilymphocyte Serum; thymoglobulin; Methotrexate; fludarabine; Cyclophosphamide; Whole-Body Irradiation; Immunosuppression Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Immunotherapy; Immunomodulation; Biological Therapy; Immunologic Techniques

Study Officials

• Michael Pulsipher, MD

  Children's Hospital Los Angeles

  STUDY CHAIR

• David A Williams, MD

  Boston's Childrens Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 9, 2016
• First Posted: July 27, 2016
• Study Start: August 1, 2016
• Primary Completion: November 3, 2020
• Study Completion: July 19, 2023
• Last Updated: May 11, 2025

Record last verified: 2024-04

Locations

US (13)