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
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|ClinicalTrials.gov Identifier: NCT00358657|
Recruitment Status : Recruiting
First Posted : August 1, 2006
Last Update Posted : November 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Immunodeficiency Syndrome Non-Cancer Diagnosis Severe Aplastic Anemia||Procedure: Allogeneic Bone Marrow Transplantation Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Drug: Sirolimus Drug: Tacrolimus Radiation: Total-Body Irradiation||Phase 2|
I. Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor.
I. Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism (> 5% cluster of differentiation [CD]3+ donor T-cell chimerism) in patients with nonmalignant inherited disorders.
II. Transplant related mortality at day 100.
III. Incidence and severity of graft-versus-host disease (GHVD).
IV. Immune reconstitution.
V. Infections during the first 200 days after HCT.
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6 and -5; and undergo total body irradiation on day -1.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on days 3 and 4, and mycophenolate mofetil orally (PO) every 8 hours on days 5-30 then twice daily (BID) to day 40, and then if there is no evidence of active GVHD and donor engraftment is > 95% (or by principal investigator [PI] approval) taper until approximately day 96, or faster at discretion of PI. Patients also receive tacrolimus IV continuously over 22-24 hours starting on day 5 post-transplant and continue on tacrolimus through day 100 followed by a taper to approximately day 180 if there is no evidence of GVHD and their graft is doing well. Patients may convert to oral tacrolimus given BID or three times daily (TID) when the patient is able to take medications orally and has a therapeutic drug level. In addition, patients will receive sirolimus orally beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well.
After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months, and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Actual Study Start Date :||May 24, 2006|
|Estimated Primary Completion Date :||June 1, 2018|
Experimental: Treatment (chemo, total-body irradiation, transplant)
See Detailed Description
Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplantation
Other Names:Drug: Cyclophosphamide
Other Names:Drug: Fludarabine Phosphate
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Mycophenolate Mofetil
Other Names:Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic bone marrow transplantation
Other Names:Drug: Sirolimus
Other Names:Drug: Tacrolimus
Given IV or PO
Other Names:Radiation: Total-Body Irradiation
Undergo total-body irradiation
- Graft rejection/failure rate [ Time Frame: Day 84 ]
- Incidence of grade III/IV acute GVHD preceding diagnosis of chronic GVHD [ Time Frame: By day 100 ]This will be deemed to occur if the lower level of a one-sided 80% confidence interval for either proportion exceeds 25% and will be evaluated after 5 patients have been followed. Adverse events will be assessed using an adapted version of the Common Toxicity Criteria.
- Transplant related mortality [ Time Frame: Day 100 ]
- Proportion of patients who achieve greater than 5% donor T-cell chimerism [ Time Frame: By day 84 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00358657
|United States, Tennessee|
|The Children's Hospital at TriStar Centennial||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact: Haydar A. Frangoul 615-329-7339 Haydar.Frangoul@hcahealthcare.com|
|Principal Investigator: Haydar A. Frangoul|
|Vanderbilt University/Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: James Connelly 615-936-1762 firstname.lastname@example.org|
|Principal Investigator: James Connelly|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Lauri M. Burroughs 206-667-2396 email@example.com|
|Principal Investigator: Lauri M. Burroughs|
|Principal Investigator:||Lauri Burroughs||Fred Hutch/University of Washington Cancer Consortium|