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 : Terminated (Low accrual)
First Posted : August 1, 2006
Results First Posted : January 26, 2021
Last Update Posted : January 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Immunodeficiency Syndrome Severe Aplastic Anemia Genetic Disorder||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 PO 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 for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 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|
|Actual Primary Completion Date :||August 17, 2018|
|Actual Study Completion Date :||May 25, 2019|
Experimental: Treatment (chemo, total-body irradiation, transplant)
See Detailed Description
Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplantation
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic bone marrow transplantation
Given IV or PO
Radiation: Total-Body Irradiation
Undergo total-body irradiation
- Graft Rejection [ Time Frame: Day 84 ]Number of patients with graft rejection (CD3 donor chimerisms <5%).
- Graft Failure [ Time Frame: Day 84 ]Number of patients with graft failure (grade IV thrombocytopenia and neutropenia after day 21 that lasts > 2 weeks andn is refractory to growth factor support).
- Proportion of Patients Who Achieve Greater Than 5% Donor T-cell Chimerism [ Time Frame: By day 84 ]Number of patients who achieve greater than 5% donor T-cell (CD3+) chimerisms
- Number of Patients With Transplant Related Mortality [ Time Frame: Day 100 post transplant ]The number of patients with transplant related mortality
- Incidence of Grade I/II Acute Graft Versus Host Disease (GVHD) [ Time Frame: Day 100 post transplant ]Number of patients diagnosed with overall GI/G2 acute GVHD by Day 100
- Incidence of Grade III/IV Acute Graft Versus Host Disease (GVHD) [ Time Frame: Day 100 post transplant ]Number of patients diagnosed with overall GIII/IV acute GVHD by Day 100
- Incidence of Chronic GVHD [ Time Frame: 1 year post transplant ]Number of patients diagnosed with chronic GVHD by 1 year post transplant
- Immune Reconstitution [ Time Frame: 1 year post transplant ]Number of patients with normal range CD3 @ 1 year post transplant
- Number of Patients With Infections [ Time Frame: Through day 200 after HCT ]Number of patients with clinically significant infections requiring treatment within 200 days after HCT
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00358657
|United States, Tennessee|
|The Children's Hospital at TriStar Centennial|
|Nashville, Tennessee, United States, 37203|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Kanwaldeep Mallhi||Fred Hutch/University of Washington Cancer Consortium|