Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

Brief Title

Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

Official Title

Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia

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.
    

Study Type

Interventional

Primary Outcome

Percentage of patients randomized to HSCT that actually complete HSCT

Secondary Outcome

 Time from screening consent to randomization

Condition

Severe Aplastic Anemia

Intervention

cyclosporine

Study Arms / Comparison Groups

 Immunosuppressive Therapy

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

40

Start Date

August 2016

Completion Date

February 2022

Primary Completion Date

February 2022

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.

          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:

          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.
      

Gender

All

Ages

N/A - 25 Years

Accepts Healthy Volunteers

No

Contacts

Michael Pulsipher, MD, 323-361-6652, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT02845596

Organization ID

TransIT NMD 1601

Responsible Party

Sponsor-Investigator

Study Sponsor

Michael Pulsipher, MD

Study Sponsor

Michael Pulsipher, MD, Study Chair, Children's Hospital Los Angeles

Verification Date

July 2021