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Severe Aplastic AnemiaNCT02845596

Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

A study testing cyclosporine, Matched Unrelated Donor Hematopoietic Stem Cell Transplant and horse anti-thymocyte globulin (ATG) in people with Severe Aplastic Anemia, run by Michael Pulsipher at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 more about this study

Who is it for?
Ages Up to 25 years
Conditions the study is for
Severe Aplastic Anemia
What is being tested?
cyclosporine, Matched Unrelated Donor Hematopoietic Stem Cell Transplant and horse anti-thymocyte globulin (ATG)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
13 sitesUnited States
Study dates
Aug 2016to 19 Jul 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
  • 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.

Who cannot join

  • 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).
Show all 9Show fewer
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Stanford Lucile Packard Children's Hospital

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Cohen Children's Medical Center

    Queens, New York, 11040

  • UCSF

    San Francisco, California, 94123

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

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.

Being tested
cyclosporine, Matched Unrelated Donor Hematopoietic Stem Cell Transplant, horse anti-thymocyte globulin (ATG), rabbit anti-thymocyte globulin (ATG), methotrexate
Medical subject headings
Anemia, Aplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cyclosporineDrug

    cyclosporine

  • Matched Unrelated Donor Hematopoietic Stem Cell TransplantProcedure or surgery

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

  • horse anti-thymocyte globulin (ATG)Drug

    Also called ATGAM

    horse anti-thymocyte globulin (ATG)

  • rabbit anti-thymocyte globulin (ATG)Drug

    Also called Thymoglobulin

    rabbit anti-thymocyte globulin (ATG)

  • methotrexateDrug

    methotrexate

  • fludarabineDrug

    fludarabine

  • cyclophosphamideDrug

    cyclophosphamide

  • low-dose total body irradiation (TBI)Radiation

    low-dose total body irradiation (TBI)

  • Immunosuppressive Therapy (IST)Procedure or surgery

    Immunosuppressive Therapy (IST)

Study groups in NCT02845596
Study groupRoleWhat they receive
Immunosuppressive TherapyActive comparatorPatient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.
Receives: Drug: cyclosporine; Drug: horse anti-thymocyte globulin (ATG); Procedure: Immunosuppressive Therapy (IST)
Matched Unrelated Stem Cell TransplantActive comparatorPatient 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.
Receives: 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)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 4 years

Secondary outcomes (18)

  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.

    Measured: 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).

    Measured: 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).

    Measured: 4 years

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

    Number of deaths that are treatment related

    Measured: 1 Year

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

    percentage of enrolled patients living at 1 year post randomization

    Measured: 1 Year

  6. Time from randomization to neutrophil recovery in both arms

    Time from randomization to neutrophil recovery in both arms

    Measured: 4 years

  7. Time from randomization to platelet recovery in both arms

    Time from randomization to platelet recovery in both arms

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 4 years

  12. Rates of IST response

    Rates of IST response

    Measured: 4 years

  13. Rates of IST relapse

    Rates of IST relapse

    Measured: 4 years

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

    Rates of secondary MDS or AML in both treatment arms.

    Measured: 4 years

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

    Rates of other secondary malignancies in both treatment arms.

    Measured: 4 years

  16. Development of symptomatic PNH in both treatment arms.

    Development of symptomatic PNH in both treatment arms.

    Measured: 4 years

  17. Incidence of significant infection in both treatment arms

    Incidence of significant infection in both treatment arms

    Measured: 4 years

  18. Time to immune reconstitution in the HSCT arm

    Time to immune reconstitution in the HSCT arm

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2016 (estimated)
  2. Study startAug 2016
  3. Primary completion3 Nov 2020
  4. Study completion19 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02845596
Sponsor's protocol ID
TransIT NMD 1601
Status last verified
Apr 2024
First submitted
9 May 2016
Last updated
11 May 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A study testing cyclosporine, Matched Unrelated Donor Hematopoietic Stem Cell Transplant and horse anti-thymocyte globulin (ATG) in people with Severe Aplastic Anemia, run by Michael Pulsipher at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients randomized to HSCT that actually complete HSCT (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02845596.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2025.

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