Stem Cell Transplantation for Sickle Cell Anemia

Hackensack Meridian Health30 enrolled

Overview

This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.

Primary objective: 1\) To determine disease free survival (DFS) at two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o Secondary objectives: 1. Overall survival 2. Rate of neutrophil and platelet engraftment for BM 3. Incidence of graft failure 4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD) 5. Incidence of chronic GVHD 6. Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS) 7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus 8. Incidence of invasive fungal disease 9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease

Interventions

AlemtuzumabDRUG

Adjusted Ideal Body Weight Formula: AIBW = IBW + \[(0.4) x (ABW - IBW)\] b) Medications i.) Alemtuzumab I. Hb S% must be \< or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued \>48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below

FludarabineDRUG

I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine

MelphalanDRUG

I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. \*Entire dose must be infused within 60 minutes of reconstitution in Pharmacy. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.

Eligibility

Sex: ALLMin age: 2 YearsMax age: 30 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient Eligibility 1\) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight) 1. Age 2-30 2. Hb SS, S-thal0, S-thal+, SC 3. Evidence of ongoing hemolysis: Hb\<10, retic \>5%, LDH \> 500, TB\>2 4. Karnofsky/Lansky score \>50 5. LVSF\>26% or LVEF\>40% 6. DLCO \>40% or O2 sat \>85% for those patients that can't perform PFTs 7. GFR \>70 and serum creatinine \< 1.5 \* ULN for age 8. ALT and AST \< 5 x ULN, direct bilirubin \<2 x ULN 9. If the patient has been on chronic transfusion or has a ferritin \>1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis * Exclusion criteria 1. Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen 2. Pregnant or breastfeeding 3. HIV positive 4. Written informed consent not obtained

Locations (1)

Hackensack University Medical Center

Hackensack, New Jersey, United States

Outcomes

Primary Outcomes

Number of Participants With Graft Failure

Primary endpoint: In each group, the Number of participants with Graft Failure at the 2 years endpoint will be estimated using the Kaplan Meier product limit estimator.

Time frame: 2 years

Secondary Outcomes

Overall Survival

Secondary endpoints: Overall survival: The distribution of time to death from any cause will be estimated by Kaplan- Meier product limit function and plotted. The overall survival will be measured from the time of transplant to any death and patients will be followed for 2 years.

Time frame: 2 years

Data from ClinicalTrials.gov

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