NCT00489281

Non-Myeloablative Bone Marrow Transplant for Patients With Sickle Cell Anemia and Other Blood Disorders

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 2 Years – 70 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

OBJECTIVES: * 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. OUTLINE: * 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.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Cyclophosphamide (Cy) 14.5 mg/kg/day intravenously (IV) on Days -6 and -5 and 50 mg/kg/day IV on Days +3 and +4.
DRUG	Fludarabine	Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.
DRUG	Mycophenolate mofetil	Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.
DRUG	Sirolimus	The first dose of Sirolimus is 6 mg PO on Day +5. Further dosing is adjusted according to drug levels. Sirolimus is continued through Day +365.
PROCEDURE	Allogeneic bone marrow transplant	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 - 200	200 centigray (cGy) in one fraction on Day -1.
DRUG	Levetiracetam	Given at 500 mg PO twice daily from Day -6 to Day +365.
BIOLOGICAL	Anti-thymocyte globulin	Test dose of 0.5 mg/kg IV given on Day -9, then 2 mg/kg/day IV on Day -8 and -7.
RADIATION	Total body irradiation - 400	400 centigray (cGy) in one fraction on Day -1.

Timeline

• Start date: 2008-06-23
• Primary completion: 2018-12-29
• Completion: 2018-12-29
• First posted: 2007-06-21
• Last updated: 2019-04-17
• Results posted: 2019-04-17

Locations

1 site across 1 country: United States