Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant in Treating Patients With Sickle Cell Anemia and Other Blood Disorders
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|ClinicalTrials.gov Identifier: NCT00489281|
Recruitment Status : Active, not recruiting
First Posted : June 21, 2007
Last Update Posted : January 30, 2017
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by a donor bone marrow transplant works in treating patients with sickle cell anemia and other blood disorders.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: Sirolimus Procedure: Allogeneic bone marrow transplantation Radiation: total-body irradiation Drug: Levetiracetam||Phase 2|
- Determine the transplant-related mortality and progression-free survival of patients with severe hemoglobinopathies receiving nonmyeloablative conditioning comprising fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by partially HLA-mismatched bone marrow transplantation from first-degree relatives or HLA-matched donors.
- Characterize donor hematopoietic chimerism at 30, 60, and 180 days after transplantation in these patients.
- Determine the hematologic and non-hematologic toxicity of this regimen in these patients.
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients also undergo total-body irradiation on day -1.
- Bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4.
- Graft-versus-host disease prophylaxis: Patients receive sirolimus orally daily on days 5-365 and oral mycophenolate mofetil 3 times a day on days 5-35.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Anemia and Other Hemoglobinopathies|
|Study Start Date :||May 2007|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||December 2018|
- Drug: cyclophosphamide
Cyclophosphamide (CTX) 14.5 mg/kg intravenously for 2 days before and after transplant.
- Drug: fludarabine phosphate
Fludarabine 30 mg/M2 intravenously for 5 days before bone marrow transplant
- Drug: mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg by mouth three times a day daily for 30 days beginning 5 days after bone marrow transplant.
- Drug: Sirolimus
The first dose of Sirolimus is 6 mg and is taken by mouth 5 days after bone marrow transplant. On the 6th day after bone marrow transplant, the dose of Sirolimus is 2 mg by mouth daily for 1 year.
- Procedure: Allogeneic bone marrow transplantation
An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.
- Radiation: total-body irradiation
Radiation of the total body will be administered the day before bone marrow transplant.
- Drug: Levetiracetam
Levetiracetam 500 mg orally twice a day 6 days before transplant and for 1 year after transplant. Levetiracetam prevents seizures.Other Name: Keppra
- Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT) [ Time Frame: 1 year after bone marrow transplant ]
- Risk-stratified estimates of 2-year progression-free survival [ Time Frame: 2 years from bone marrow transplant ]
- Time to recovery of circulating neutrophils and platelets after chemotherapy [ Time Frame: 60 days from bone marrow transplant ]
- Donor chimerism at 30, 60, 180, and 365 days after bone marrow transplant [ Time Frame: 1 year from bone marrow transplant ]
- Development of graft-vs-host disease [ Time Frame: 1 year from bone marrow transplant ]
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): NCT00489281
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Study Chair:||Javier Bolanos-Meade, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|