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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00489281
Recruitment Status : Active, not recruiting
First Posted : June 21, 2007
Last Update Posted : January 30, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief 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.

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

Detailed Description:


  • 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)
Primary Purpose: Treatment
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

Intervention Details:
  • 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

Primary Outcome Measures :
  1. Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT) [ Time Frame: 1 year after bone marrow transplant ]
  2. Risk-stratified estimates of 2-year progression-free survival [ Time Frame: 2 years from bone marrow transplant ]

Secondary Outcome Measures :
  1. Time to recovery of circulating neutrophils and platelets after chemotherapy [ Time Frame: 60 days from bone marrow transplant ]
  2. Donor chimerism at 30, 60, 180, and 365 days after bone marrow transplant [ Time Frame: 1 year from bone marrow transplant ]
  3. Development of graft-vs-host disease [ Time Frame: 1 year from bone marrow transplant ]

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes


  • 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


  • 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


  • No prior transfusions from donor
  • No immunosuppressive agents, including steroids as antiemetics, within 24 hours after the last dose of post-transplantation cyclophosphamide

Information from the National Library of Medicine

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 identifier (NCT number): NCT00489281

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Study Chair: Javier Bolanos-Meade, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00489281     History of Changes
Other Study ID Numbers: J0676 CDR0000540593
P30CA006973 ( U.S. NIH Grant/Contract )
P01CA015396 ( U.S. NIH Grant/Contract )
First Posted: June 21, 2007    Key Record Dates
Last Update Posted: January 30, 2017
Last Verified: January 2017

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
sickle cell disease

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Fludarabine phosphate
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antibiotics, Antitubercular