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CompletedNCT02845596Updated May 11, 2025

Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

An interventional study of cyclosporine and Matched Unrelated Donor Hematopoietic Stem Cell Transplant in Severe Aplastic Anemia, sponsored by Michael Pulsipher. Completed at 13 sites in United States. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2025-05-11.

Sponsored by Michael Pulsipher · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
Up to 25 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Severe Aplastic Anemia
03

In context

Anemia

1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.

This study's planned enrollment of 40 is below the median of 94 across 1,291 interventional studies indexed under Anemia.

Browse Anemia studies →

Lead sponsor

Michael Pulsipher is the lead sponsor of 3 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 25 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.
  6. Adequate organ function defined as in the judgment of the investigator, there is not irreversible organ damage that would preclude the patient from meeting the organ function inclusion criteria for HSCT listed in section 2.3.4 by the intended time of HSCT (6-8 weeks after randomization) or preclude patients from receiving horse ATG.

Exclusion criteria

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.
05

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (estimated)

Study arms

  • Active comparator
    Immunosuppressive Therapy

    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)

  • Active comparator
    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.

    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

  • Drugcyclosporine

    cyclosporine

  • ProcedureMatched Unrelated Donor Hematopoietic Stem Cell Transplant

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

  • Drughorse anti-thymocyte globulin (ATG)

    horse anti-thymocyte globulin (ATG)

    Also known as: ATGAM

  • Drugrabbit anti-thymocyte globulin (ATG)

    rabbit anti-thymocyte globulin (ATG)

    Also known as: Thymoglobulin

  • Drugmethotrexate

    methotrexate

  • Drugfludarabine

    fludarabine

  • Drugcyclophosphamide

    cyclophosphamide

  • Radiationlow-dose total body irradiation (TBI)

    low-dose total body irradiation (TBI)

  • ProcedureImmunosuppressive Therapy (IST)

    Immunosuppressive Therapy (IST)

06

What researchers measure

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.

    Time frame: 4 years

Secondary outcomes

  1. Time from screening consent to randomization

    To measure the time from screening consent and randomization of patients to initiation of the preparative regimen of those randomized to HSCT.

    Time frame: 4 years

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

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

    Time frame: 4 years

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

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

    Time frame: 4 years

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

    Number of deaths that are treatment related

    Time frame: 1 Year

  5. Overall Survival at one year from randomization in both arms

    percentage of enrolled patients living at 1 year post randomization

    Time frame: 1 Year

  6. Time from randomization to neutrophil recovery in both arms

    Time from randomization to neutrophil recovery in both arms

    Time frame: 4 years

  7. Time from randomization to platelet recovery in both arms

    Time from randomization to platelet recovery in both arms

    Time frame: 4 years

  8. Time from randomization to red blood cell recovery in both arms

    Time from randomization to red blood cell recovery in both arms

    Time frame: 4 years

  9. Time from randomization to cessation of immune suppression recovery in both arms

    Time from randomization to cessation of immune suppression recovery in both arms

    Time frame: 4 years

  10. Rates of primary and secondary graft rejection in the MUD HSCT arm

    Rates of primary and secondary graft rejection in the MUD HSCT arm

    Time frame: 4 years

  11. Rates of grade II-IV and III-IV acute GVHD, and extensive chronic GVHD in the MUD HSCT arm

    Rates of grade II-IV and III-IV acute GVHD, and extensive chronic GVHD in the MUD HSCT arm

    Time frame: 4 years

  12. Rates of IST response

    Rates of IST response

    Time frame: 4 years

  13. Rates of IST relapse

    Rates of IST relapse

    Time frame: 4 years

  14. Rates of secondary MDS or AML in both treatment arms.

    Rates of secondary MDS or AML in both treatment arms.

    Time frame: 4 years

  15. Rates of other secondary malignancies in both treatment arms.

    Rates of other secondary malignancies in both treatment arms.

    Time frame: 4 years

  16. Development of symptomatic PNH in both treatment arms.

    Development of symptomatic PNH in both treatment arms.

    Time frame: 4 years

  17. Incidence of significant infection in both treatment arms

    Incidence of significant infection in both treatment arms

    Time frame: 4 years

  18. Time to immune reconstitution in the HSCT arm

    Time to immune reconstitution in the HSCT arm

    Time frame: 4 years

07

Study locations

13 sites
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • Stanford Lucile Packard Children's Hospital
    Palo Alto, California 94304, United States
  • UCSF
    San Francisco, California 94123, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Cohen Children's Medical Center
    Queens, New York 11040, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • UT Southwestern Medical Center
    Dallas, Texas 75390, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • Fred Hutchinson Cancer Research Center
    Seattle, Washington 98109, United States
  • University of Wisconsin
    Madison, Wisconsin 53792, United States
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 11, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02845596
Lead sponsor
Michael Pulsipher
Responsible party
Michael Pulsipher (Principal Investigator, Pediatric Transplantation & Cellular Therapy Consortium) — Sponsor-investigator
First posted
Jul 27, 2016
Start date
Aug 2016
Primary completion
Nov 3, 2020
Completion
Jul 19, 2023
Last update
May 11, 2025

Study contacts

Michael Pulsipher, MD
study chair · Children's Hospital Los Angeles
David A Williams, MD
study chair · Boston's Childrens Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2024. You cannot join it, but the record below documents what was studied.

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