Stem Cell Transplantation for Sickle Cell Anemia

Phase 3

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: Alemtuzumab; Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cells

• Registration Number: NCT01877837
• Lead Sponsor: Hackensack Meridian Health

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2011-06
• Study First Submitted: 2013-06-12
• Study First Submitted QC: 2013-06-13
• Study First Posted: 2013-06-14
• Primary Completion: 2021-09
• Study Completion: 2021-09
• Results First Submitted: 2022-09-07
• Status Verified: 2022-10
• Results First Submitted QC: 2022-10-12
• Last Update Submitted: 2022-10-12
• Results First Posted: 2022-11-07
• Last Update Posted: 2022-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Related donor	Stem Cells	Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan. 1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below. Day Treatment * -22 Alemtuzumab 3mg IV (test dose) * -21 Alemtuzumab 10mg IV * -20 Alemtuzumab 15mg IV * -19 Alemtuzumab 20mg IV * -8 Fludarabine 30mg/m2 IV * -7 Fludarabine 30mg/m2 IV * -6 Fludarabine 30mg/m2 IV * -5 Fludarabine 30mg/m2 IV * -4 Fludarabine 30mg/m2 IV * -3 Melphalan 140mg/m2 IV * -2 Rest Day * -1 Rest Day * 0 Stem Cell Infusion
Related donor	Alemtuzumab	Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan. 1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below. Day Treatment * -22 Alemtuzumab 3mg IV (test dose) * -21 Alemtuzumab 10mg IV * -20 Alemtuzumab 15mg IV * -19 Alemtuzumab 20mg IV * -8 Fludarabine 30mg/m2 IV * -7 Fludarabine 30mg/m2 IV * -6 Fludarabine 30mg/m2 IV * -5 Fludarabine 30mg/m2 IV * -4 Fludarabine 30mg/m2 IV * -3 Melphalan 140mg/m2 IV * -2 Rest Day * -1 Rest Day * 0 Stem Cell Infusion
Related donor	Fludarabine	Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan. 1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below. Day Treatment * -22 Alemtuzumab 3mg IV (test dose) * -21 Alemtuzumab 10mg IV * -20 Alemtuzumab 15mg IV * -19 Alemtuzumab 20mg IV * -8 Fludarabine 30mg/m2 IV * -7 Fludarabine 30mg/m2 IV * -6 Fludarabine 30mg/m2 IV * -5 Fludarabine 30mg/m2 IV * -4 Fludarabine 30mg/m2 IV * -3 Melphalan 140mg/m2 IV * -2 Rest Day * -1 Rest Day * 0 Stem Cell Infusion
Related donor	Melphalan	Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan. 1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below. Day Treatment * -22 Alemtuzumab 3mg IV (test dose) * -21 Alemtuzumab 10mg IV * -20 Alemtuzumab 15mg IV * -19 Alemtuzumab 20mg IV * -8 Fludarabine 30mg/m2 IV * -7 Fludarabine 30mg/m2 IV * -6 Fludarabine 30mg/m2 IV * -5 Fludarabine 30mg/m2 IV * -4 Fludarabine 30mg/m2 IV * -3 Melphalan 140mg/m2 IV * -2 Rest Day * -1 Rest Day * 0 Stem Cell Infusion

Primary Outcome Measures

Name	Time	Method
Number of Participants With Graft Failure	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years	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.

Trial Locations

Locations (1)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States