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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT02845596
Date of registration: 09/05/2016
Prospective Registration: Yes
Primary sponsor: Michael Pulsipher, MD
Public title: Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia
Scientific title: Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia
Date of first enrolment: August 2016
Target sample size: 40
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT02845596
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: None (Open Label).  
Phase:  N/A
Countries of recruitment
United States
Contacts
Name:     Liz Gourdine
Address: 
Telephone: 323-361-6652
Email: TransIT@chla.usc.edu
Affiliation: 
Name:     David A Williams, MD
Address: 
Telephone:
Email:
Affiliation:  Boston's Childrens Hospital
Name:     Michael Pulsipher, MD
Address: 
Telephone:
Email:
Affiliation:  Children's Hospital Los Angeles
Key inclusion & exclusion 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.



Age minimum: N/A
Age maximum: 25 Years
Gender: All
Health Condition(s) or Problem(s) studied
Severe Aplastic Anemia
Intervention(s)
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine
Drug: horse anti-thymocyte globulin (ATG)
Drug: methotrexate
Drug: rabbit anti-thymocyte globulin (ATG)
Procedure: Immunosuppressive Therapy (IST)
Procedure: Matched Unrelated Donor Hematopoietic Stem Cell Transplant
Radiation: low-dose total body irradiation (TBI)
Primary Outcome(s)
Percentage of patients randomized to HSCT that actually complete HSCT [Time Frame: 4 years]
Secondary Outcome(s)
Development of symptomatic PNH in both treatment arms. [Time Frame: 4 years]
Incidence of significant infection in both treatment arms [Time Frame: 4 years]
Number of patients that fail to receive their primary assigned therapy (HSCT or IST). [Time Frame: 4 years]
Overall Survival at one year from randomization in both arms [Time Frame: 1 Year]
Rates of grade II-IV and III-IV acute GVHD, and extensive chronic GVHD in the MUD HSCT arm [Time Frame: 4 years]
Rates of IST relapse [Time Frame: 4 years]
Rates of IST response [Time Frame: 4 years]
Rates of other secondary malignancies in both treatment arms. [Time Frame: 4 years]
Rates of primary and secondary graft rejection in the MUD HSCT arm [Time Frame: 4 years]
Rates of secondary MDS or AML in both treatment arms. [Time Frame: 4 years]
Reasons why patients fail to receive their primary assigned therapy (HSCT or IST). [Time Frame: 4 years]
Time from randomization to cessation of immune suppression recovery in both arms [Time Frame: 4 years]
Time from randomization to neutrophil recovery in both arms [Time Frame: 4 years]
Time from randomization to platelet recovery in both arms [Time Frame: 4 years]
Time from randomization to red blood cell recovery in both arms [Time Frame: 4 years]
Time from screening consent to randomization [Time Frame: 4 years]
Time to immune reconstitution in the HSCT arm [Time Frame: 4 years]
Treatment-related mortality at one year from randomization in both arms [Time Frame: 1 Year]
Secondary ID(s)
TransIT NMD 1601
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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