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Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia

This study has been terminated.
(Due to slow recruitment)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID) Identifier:
First received: April 30, 2002
Last updated: April 30, 2013
Last verified: April 2013

The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.

Condition Intervention Phase
Anemia, Sickle Cell
Hemoglobin SC Disease
Thalassemia Major
Drug: Busulfan
Drug: Fludarabine
Drug: FK506
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation Following Nonmyeloablative Chemotherapy in Patients With Hemoglobinopathies

Resource links provided by NLM:

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Solid organ toxicity related to the conditioning regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Incidence of grade II, III, or IV acute graft versus host disease (GVHD) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Level of disease response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: September 2001
Study Completion Date: November 2003
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic stem cell transplantation
Participants will receive a nonmyeloablative conditioning regimen of fludarabine and busulfan prior to allogeneic peripheral blood stem cell (CD34+) infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis.
Drug: Busulfan
0.8 mg/kg/d administered as a single intravenous infusion over 3 hours for 4 days. All infusions are anticipated to be given in the outpatient clinic.
Other Name: Busulfex
Drug: Fludarabine
30 mg/m^2/d administered as a bolus infusion over 30 minutes for 4 days. All infusions are anticipated to be given in the outpatient clinic.
Other Names:
  • Fludara
  • Oforta
Drug: FK506
0.15 mg/kg taken orally daily for 12 to 14 weeks
Other Names:
  • Prograf
  • Tacromilus
Drug: Prednisone
0.5 mg/kg taken orally four times daily on Day 7 and increase to 1 mg/kg taken orally four times daily on Day 14. Participants will continue regimen until Day 30 before a 20-25% taper per week.

Detailed Description:

Hemoglobinopathies, such as sickle cell disease and thalassemia major, are genetic diseases associated with significant morbidity and premature death. Allogeneic bone marrow transplantation (BMT) is the only potential cure for severe hemoglobinopathies. Typical regimens have used high doses of chemotherapy or chemo-radiotherapy to ablate recipient hematopoiesis and to prevent graft rejection. The widespread use of this treatment has been limited by toxicity, risk of end-organ damage, and donor availability. This study will use a nonmyeloablative regimen of fludarabine and busulfan to attempt to generate consistent engraftment with donor hematopoietic stem cells in patients with severe hemoglobinopathy.

G-CSF mobilization of the donor's peripheral blood white blood cells will precede donor apheresis. A nonmyeloablative conditioning regimen of fludarabine and busulfan will be administered to patients prior to allogeneic peripheral blood stem cell infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis. Patients will be evaluated for engraftment, donor: host hematopoietic chimerism, toxicity, and hemoglobinopathy.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • All patients must:

    • Have related donors who are identical at 6 human leukocyte antigens (HLA) loci (A, B and DR) by molecular typing
    • Have a performance status from 0-2
    • Give written informed consent
  • Patients with sickle cell disease should have 1 or more of the following:

    • Acute chest syndrome requiring recurrent hospitalization or exchange transfusion
    • Nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours
    • Recurrent vaso-occlusive pain (2 episodes or more per year) or recurrent priapism
    • Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50 percent of normal predicted value)
    • Bilateral proliferative retinopathy and major visual impairment in at least 1 eye
    • Osteonecrosis of multiple joints
  • Patients with thalassemia should have 1 or more of the following:

    • Transfusion dependence, defined as a transfusion requirement of greater than or equal to 6 units of packed red blood cells over the past 12 months
    • Iron overload, defined as serum ferritin greater than 500 mcg/L in the absence of infection or biopsy-proven iron overload
    • Presence of 2 or more alloantibodies against red cell antigens

Exclusion criteria:

  • Pregnancy
  • Acute hepatitis (transaminases greater than 3 times the normal value)
  • Cardiac ejection fraction less than 30 percent
  • Severe renal impairment (glomerular filtration rate less than 30 percent of predicted normal value)
  • Severe residual functional neurologic impairment (other than hemiplegia alone)
  • Seropositivity for the human immunodeficiency virus (HIV)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00034528

United States, Massachusetts
Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Principal Investigator: Catherine J. Wu, MD Dana Farber Cancer Institute/Harvard Medical School
  More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00034528     History of Changes
Other Study ID Numbers: DAIT DF/HCC 01-098, P01 A 129530
Study First Received: April 30, 2002
Last Updated: April 30, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Anemia, Sickle Cell
Hemoglobin C Disease
Hemoglobin SC Disease
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Fludarabine phosphate
Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on February 26, 2015