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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Terminated; Phase 2

Conditions: Thalassemia; Hemoglobinopathies; Anemia, Sickle Cell; Thalassemia Major; Hemoglobin SC Disease

Treatments: Drug: Fludarabine; Drug: Busulfan; Drug: FK506; Drug: Prednisone

Study type: Interventional

Funder types: NIH

Identifiers

NCT00034528

DAIT DF/HCC 01-098

P01 A 129530

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Allogeneic stem cell transplantation

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Drug: FK506

Drug: Prednisone

Drug: Busulfan