SCDHCT: Reduced Intensity Related Donor HCT for Patients with Severe Sickle Cell Disease [CLOSED TO ACCRUAL]

This study evaluates a reduced intensity conditioning-based hematopoietic cell transplantation (HCT) in children and young adults with sickle cell disease (SCD) who either have an HLA-matched sibling donor or a single haplotype matched (half matched) family member donor.

Patients with severe SCD who would be expected to benefit from an HCT will undergo a reduced intensity conditioning regimen of alemtuzumab, thiotepa and low-dose total body irradiation, followed by unmanipulated peripheral blood-derived hematopoietic stem and progenitor cell graft from a donor. All patients in the study will receive a pre-conditioning phase comprised of hydroxyurea and azathioprine to reduce the risk of graft rejection.

Primary objective

• To assess the donor T-cell chimerism at 1-year after transplant in each respective arm of the trial

Secondary Objectives

• Assess overall survival and 1-year, 2-year and 3-year post-transplant GVHD-free SCD-free survival
• Estimate the primary and secondary graft rejection rate at 1-year, 2-year and 3-year post-transplant
• Estimate the incidence and severity of acute and chronic GVHD
• Estimate the incidence of SCD recurrence after transplant
• Assess the neutrophil and platelet recovery kinetics post-transplant

Eligibility Criteria

Inclusion criteria for transplant recipient include:

• 25 years old or younger
• Diagnosis of sickle cell disease (any genotype) and ONE of the following:
  • History of abnormal transcranial Doppler measurement
  • History of cerebral infarction on brain MRI
  • History of two or more episodes of acute chest syndrome in the prior two years
  • History of two or more SCD pain events requiring treatment with an opiate or IV pain medication in the last 12 months
  • History of any hospitalization for SCD pain or acute chest syndrome while receiving hydroxyurea in the last 12 months
  • History of two or more episodes of erection lasting 4 or more hours or requiring emergent care
  • Administration of 8 or more red blood cell transfusions in the previous 12 months
  • At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration

Exclusion criteria for transplant recipient include:

• Pregnant or breastfeeding
• Karnofsky or Lansky performance score below 60
• Uncontrolled bacterial, viral or fungal infections within 1 month prior to conditioning

Inclusion criteria for donor include:

• HLA-matched sibling donor or single haplotype matched family member
• HIV negative
• Not pregnant or breastfeeding
• Does not have clinically significant hemoglobinopathy

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

About this study

This study is being done to test a transplant method that may have fewer side effects or be less toxic than standard transplants that use high-dose chemotherapy for children and young adults with sickle cell disease.

Sickle cell disease symptoms are usually treated by giving the medicine hydroxyurea and/or regular red blood cell transfusions. These treatments have improved survival in patients with sickle cell disease. Performing a transplant of blood-forming cells from a donor may provide a cure for this disease. However, getting a transplant can have many bad side effects.

Normally, patients undergoing this type of blood transplant for sickle cell disease receive high-dose chemotherapy to prepare the body for the transplant. Researchers leading this study want to see if a different conditioning treatment works just as well with fewer side effects. This new method uses fewer drugs to suppress your immune system before transplant.

Purpose of this clinical trial

The main goal of this study is to see if this new method decreases sickle cell disease symptoms and reduces treatment-related side effects.

Eligibility overview

• 25 years old or younger
• Diagnosed with severe sickle cell disease
• Has a suitable HLA-matched sibling donor or single haplotype matched family member donor