Non-Myeloablative Bone Marrow Transplant for Patients With Sickle Cell Anemia and Other Blood Disorders
NCT ID: NCT00489281
Last Updated: 2019-04-17
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
43 participants
INTERVENTIONAL
2008-06-23
2018-12-29
Brief Summary
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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.
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Detailed Description
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* 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
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Transplant - 200 cGy
Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 200. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
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.
Fludarabine
Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.
Mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.
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.
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.
Total body irradiation - 200
200 centigray (cGy) in one fraction on Day -1.
Levetiracetam
Given at 500 mg PO twice daily from Day -6 to Day +365.
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.
Transplant - 400 cGy
Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 400. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
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.
Fludarabine
Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.
Mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.
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.
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.
Levetiracetam
Given at 500 mg PO twice daily from Day -6 to Day +365.
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.
Total body irradiation - 400
400 centigray (cGy) in one fraction on Day -1.
Interventions
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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.
Fludarabine
Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.
Mycophenolate mofetil
Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.
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.
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.
Total body irradiation - 200
200 centigray (cGy) in one fraction on Day -1.
Levetiracetam
Given at 500 mg PO twice daily from Day -6 to Day +365.
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.
Total body irradiation - 400
400 centigray (cGy) in one fraction on Day -1.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* No minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available
PATIENT CHARACTERISTICS:
* ECOG performance status (PS) 0-1 OR Karnofsky or Lansky PS 70-100%
* LVEF ≥ 35%
* FEV\_1 and forced vital capacity ≥ 40% predicted
* Direct bilirubin \< 3.1 mg/dL
* No moderate to severe pulmonary hypertension by ECHO
* No debilitating medical or psychiatric illness that would preclude study participation
* No HIV positivity
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
* No prior transfusions from donor
* No immunosuppressive agents, including steroids as antiemetics, within 24 hours after the last dose of post-transplantation cyclophosphamide
2 Years
70 Years
ALL
Yes
Sponsors
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National Cancer Institute (NCI)
NIH
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
OTHER
Responsible Party
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Principal Investigators
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Javier Bolanos-Meade, MD
Role: STUDY_CHAIR
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Locations
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Countries
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References
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Bolanos-Meade J, Cooke KR, Gamper CJ, Ali SA, Ambinder RF, Borrello IM, Fuchs EJ, Gladstone DE, Gocke CB, Huff CA, Luznik L, Swinnen LJ, Symons HJ, Terezakis SA, Wagner-Johnston N, Jones RJ, Brodsky RA. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019 Apr;6(4):e183-e193. doi: 10.1016/S2352-3026(19)30031-6. Epub 2019 Mar 14.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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