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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.
Last refreshed on: 12 December 2020
Main ID:  NCT00358657
Date of registration: 28/07/2006
Prospective Registration: Yes
Primary sponsor: Fred Hutchinson Cancer Research Center
Public title: Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders
Scientific title: HLA-Haploidentical Related Marrow Grafts for the Treatment of Primary Immunodeficiencies and Other Nonmalignant Disorders Using Conditioning With Low-Dose Cyclophosphamide, TBI and Fludarabine and Postgrafting Cyclophosphamide
Date of first enrolment: May 24, 2006
Target sample size: 14
Recruitment status: Active, not recruiting
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     Kanwaldeep Mallhi
Affiliation:  Fred Hutch/University of Washington Cancer Consortium
Key inclusion & exclusion criteria

Inclusion Criteria:

- Primary immunodeficiency disorder or other nonmalignant inherited disease (except
Fanconi anemia) treatable by allogeneic HCT

- Patients with pre-existing medical conditions or other factors that renders them at
high risk for regimen related toxicity or ineligible for conventional myeloablative
HCT and who do not have HLA-matched related or unrelated donors

- Patients with a related donor who is identical for one HLA haplotype

- Acquired aplastic anemia: severe aplastic anemia (SAA) is defined as follows:

- Bone marrow cellularity < 25%, or marrow cellularity < 50% but with < 30%
residual hematopoietic cells

- Two out of three of the following (in peripheral blood): neutrophils < 0.5 x
10^9/L; platelets < 20 x 10^9/L; reticulocytes < 20 x 10^9/L

- SAA diagnostic criteria may be applied to assessment at initial diagnosis or
follow-up assessments

- DONOR: Related donors who are identical for one HLA haplotype

- DONOR: Bone marrow will be the only allowed stem cell source

Exclusion Criteria:

- Fanconi anemia

- Suitably HLA-matched related or unrelated donors

- Patients with metabolic storage diseases who have severe central nervous system (CNS)
involvement of disease, defined as intelligence quotient (IQ) score < 70

- Cardiac ejection fraction < 30% (or, if unable to obtain ejection fraction, shortening
fraction < 26%) on multiple-gated acquisition (MUGA) scan or cardiac echocardiogram
(echo), symptomatic coronary artery disease, or other cardiac failure requiring
therapy; patients with a history of, or current cardiac disease should be evaluated
with appropriate cardiac studies and/or cardiology consult; patients with a shortening
fraction of < 26% must be seen by cardiology for approval

- Poorly controlled hypertension despite anti-hypertensive medications

- Patients with clinical or laboratory evidence of liver disease will need to be
evaluated for the cause of the liver disease, its clinical severity in terms of liver
function and the degree of portal hypertension; patients will be excluded if they are
found to have fulminant liver failure, cirrhosis of the liver with evidence of portal
hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of
bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic
dysfunction evidenced by prolongation of the prothrombin time, ascites related to
portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic
viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease

- Positive for human immunodeficiency virus (HIV)

- Females who are pregnant (beta-human chorionic gonadotropin positive [beta-HCG+]) or

- Fertile men or women who are unwilling to use contraceptives during HCT and up to 12
months post-treatment

- Patients with fungal pneumonia with radiological progression after receipt of
amphotericin formulation or mold-active azoles for greater than 1 month will not be
eligible for this protocol (either regimen A or B)

- DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the
host-versus-graft (HVG) direction; patients are homozygous and donor is heterozygous

- DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1
x 10^8 nucleated cells/kg recipient ideal body weight)

- DONOR: HIV-positive donors

- DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion

- DONOR: < 6 months old and > 75 years old

Age minimum: N/A
Age maximum: 55 Years
Gender: All
Health Condition(s) or Problem(s) studied
Immunodeficiency Syndrome
Non-Cancer Diagnosis
Severe Aplastic Anemia
Drug: Cyclophosphamide
Drug: Fludarabine Phosphate
Drug: Mycophenolate Mofetil
Drug: Sirolimus
Drug: Tacrolimus
Other: Laboratory Biomarker Analysis
Procedure: Allogeneic Bone Marrow Transplantation
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Radiation: Total-Body Irradiation
Primary Outcome(s)
Graft rejection/failure rate [Time Frame: Day 84]
Incidence of grade III/IV acute graft versus host disease (GVHD) preceding diagnosis of chronic GVHD [Time Frame: By day 100]
Transplant related mortality [Time Frame: Day 100]
Secondary Outcome(s)
Proportion of patients who achieve greater than 5% donor T-cell chimerism [Time Frame: By day 84]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Ethics review
Results available:
Date Posted:
Date Completed:
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