Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant in Treating Patients With Sickle Cell Anemia and Other Blood Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00489281
First received: June 20, 2007
Last updated: September 29, 2014
Last verified: September 2014

June 20, 2007
September 29, 2014
May 2007
May 2016   (final data collection date for primary outcome measure)
  • Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT) [ Time Frame: 1 year after bone marrow transplant ] [ Designated as safety issue: No ]
  • Risk-stratified estimates of 2-year progression-free survival [ Time Frame: 2 years from bone marrow transplant ] [ Designated as safety issue: No ]
  • Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT)
  • Risk-stratified estimates of 2-year progression-free survival
Complete list of historical versions of study NCT00489281 on ClinicalTrials.gov Archive Site
  • Time to recovery of circulating neutrophils and platelets after chemotherapy [ Time Frame: 60 days from bone marrow transplant ] [ Designated as safety issue: No ]
  • Donor chimerism at 30, 60, 180, and 365 days after bone marrow transplant [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
  • Development of graft-vs-host disease [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
  • Time to recovery of circulating neutrophils and platelets after chemotherapy
  • Donor chimerism at 30, 60, and 180 days after BMT
  • Development of graft-vs-host disease
Not Provided
Not Provided
 
Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant in Treating 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

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Sickle Cell Disease
  • 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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
Not Provided
May 2016   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following sickle cell anemias (Hb SS):

    • Hb S/β° thalassemia
    • Hb S/β+ thalassemia
    • Hb SC disease
    • Hb SE disease
    • Hb SD disease
    • Hemoglobin SO-Arab disease
    • Hb S/hereditary persistence of fetal hemoglobin
  • Meets 1 of the following criteria:

    • History of invasive pneumococcal disease
    • Stroke or CNS event lasting > 24 hours
    • MRI changes indicative of brain parenchymal damage
    • Evidence of cerebrovascular disease by magnetic resonance angiography
    • Acute chest syndrome requiring exchange transfusion or hospitalization
    • Recurrent vaso-occlusive pain crisis (> 2 per year for the last 2 years)
    • Stage I or II sickle lung disease
    • Sickle retinopathy
    • Osteonecrosis
    • Red cell alloimmunization (> 2 antibodies) during long-term transfusion
    • Constellation of dactylitis in the first year of life AND a baseline hemoglobin < 7 g/dL and leukocytosis (WBC > 13.4/mm^3) in the absence of infection during the second year of life
    • Pitted RBC count > 3.5% during the first year of life
  • Ineligible for or refused bone marrow transplantation from an HLA-matched sibling donor
  • Partially mismatched (at least haploidentical) first-degree relative donor available

    • 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
Both
2 Years to 70 Years
Yes
United States
 
NCT00489281
J0676 CDR0000540593, P30CA006973, P01CA015396, JHOC-J0676, JHOC-NA_00002479
Not Provided
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Javier Bolanos-Meade, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP