Reduced Intensity Related Donor Peripheral Blood Derived Hematopoietic Progenitor Cell Transplantation for Patients With Severe Sickle Cell Disease

Study point of contact

Akshay Sharma, MBBS
[email protected]


1 United States site


2 to 25 Years


Phase 2

Study type








About the study

This study is being done to test a transplant method that may have fewer side effects (or
less toxic, less harmful) than conventional high dose chemotherapy conditioning-based
transplants for children and young adults with Sickle Cell Disease (SCD). Patients less than
or equal to 25 years old with SCD who would likely benefit from allogeneic hematopoietic cell
transplantation (HCT) will be included in this study. Patients with a suitable HLA matched
sibling donor (MSD) will be enrolled on the MSD arm while patients without an eligible MSD
who have a suitable haploidentical (HAPLO) donor available will be enrolled on the HAPLO arm
of the study.

Primary Objective

To assess the donor T-cell chimerism at 1-year post transplant in each respective arm (MSD,
HAPLO) of the trial.

Secondary Objectives

– Assess the overall survival and 1-year, 2-year and 3-year post-transplant graft versus
host disease (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.

Exploratory Objectives

– Record immune reconstitution parameters, including chimerism analysis, quantitative
lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta
spectratyping, and lymphocyte phenotype and function.

– Conduct longitudinal examination of impact of HCT on patient health-related quality of
life (HRQL) and adjustment, and parental adjustment.

– Examine impact of HCT on patient cognitive and academic function.

– Determine factors that influenced the decision to undergo HCT, explore perceptions of
the HCT experience, and assess decisional satisfaction/regret.

– Develop and evaluate an objective/quantitative imaging biomarker to assess organ (liver
and heart) function/disease status and changes following HCT.

– Develop and evaluate an objective/quantitative imaging biomarker to determine cerebral
blood flow and oxygen extraction fraction following HCT.

participation requirements

for Transplant Recipient

– Age less than or equal to 25 years.

– Patients with a suitable HLA-matched sibling donor (MSD) can be enrolled on MSD arm of
the trial. Patients with single haplotype matched (≥ 3 of 6) family member donor can
be enrolled on HAPLO arm of the trial, if they do not have a suitable HLA-matched
sibling donor (MSD) available for progenitor cell donation.

– Patients with SCD (any genotype) who meet any ONE of the following criteria:

1. History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥
200 cm/sec by the non-imaging technique (or ≥ 185 cm/sec by the imaging
technique) measured at a minimum of two separate occasions.

2. History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3
mm in one dimension, visible in two planes on fluid-attenuated inversion recovery
T2- weighted images).

3. History of two or more episodes of acute chest syndrome (ACS) in the 2-years
period preceding enrollment.

4. History of two or more SCD pain events requiring treatment with an opiate or IV
pain medication (inpatient or outpatient) in the last 12 months.

5. History of any hospitalization for SCD pain or ACS while receiving hydroxyurea
treatment in the last 12 months.

6. History of two or more episodes of priapism (erection lasting ≥4 hours or
requiring emergent medical care).

7. Administration of regular RBC transfusions (≥8 transfusions in the previous 12

8. At least two episodes of splenic sequestration requiring red blood cell
transfusion or splenectomy after at least one episode of splenic sequestration.

participation restrictions

for Transplant Recipient

– Karnofsky or Lansky performance score <60. - Pregnant or breastfeeding patients. - Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity or positive NAAT for HIV are excluded. - Serum conjugated (direct) bilirubin >3x upper limit of normal for age or serum ALT >5x
upper limit of normal for age as per local laboratory. Participants with
hyperbilirubinemia or elevated AST as the result of hyperhemolysis, or a severe drop
in hemoglobin post blood transfusion, are not excluded as long as these values
downtrend and return to acceptable limits subsequently.

– Left ventricular shortening fraction <25% or ejection fraction <40% by echocardiogram. - Estimated creatinine clearance less than 50 mL/min/1.73m2. - Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin). Baseline oxygen saturation <85% or PaO2 <70. - History of RBC alloantibodies against donor RBC antigens (even if current antibody screen is negative). - Presence of high titer anti-donor specific HLA antibodies should be carefully evaluated, and desensitization considered prior to transplantation. HLA antibody presence and specificity will be determined by solid phase immunoassays. An anti-donor specific HLA antibody will be considered positive when the mean fluorescence intensity (MFI) is >1000 for donor specific antibody to HLA-A, -B, and DRB1 and MFI >2000 for
HLA-C, DQB1 and DPB1. Patients with borderline elevated anti-donor specific HLA
antibodies may be considered for inclusion in consultation with the PIs.


  • Memphis, Tennessee, United States, St. Jude Children's Research Hospital, 38105 [Recruiting]