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Stem Cell Transplantation for Sickle Cell Anemia

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab
Fludarabine
Melphalan
Stem Cells
Sponsored by
Hackensack Meridian Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Stem cell transplant, Sickle cell, Stem cell transplantation, Related, Unrelated

Eligibility Criteria

2 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hackensack University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Related donor

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 12, 2013
Last Updated
October 12, 2022
Sponsor
Hackensack Meridian Health
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1. Study Identification

Unique Protocol Identification Number
NCT01877837
Brief Title
Stem Cell Transplantation for Sickle Cell Anemia
Official Title
Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
September 2021 (Actual)
Study Completion Date
September 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: Overall survival Rate of neutrophil and platelet engraftment for BM Incidence of graft failure Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD) Incidence of chronic GVHD Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS) Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus Incidence of invasive fungal disease Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Stem cell transplant, Sickle cell, Stem cell transplantation, Related, Unrelated

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Related donor
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Alemtuzumab (Campath)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabine (Fludara)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Melphalan (Alkeran)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Stem Cells
Intervention Description
Infusion of Hematopoietic Stem Cells
Primary Outcome Measure Information:
Title
Number of Participants With Graft Failure
Description
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 Outcome Measure Information:
Title
Overall Survival
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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) Age 2-30 Hb SS, S-thal0, S-thal+, SC Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2 Karnofsky/Lansky score >50 LVSF>26% or LVEF>40% DLCO >40% or O2 sat >85% for those patients that can't perform PFTs GFR >70 and serum creatinine < 1.5 * ULN for age ALT and AST < 5 x ULN, direct bilirubin <2 x ULN 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 Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen Pregnant or breastfeeding HIV positive Written informed consent not obtained
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Krajewski, MD
Organizational Affiliation
Hackensack Meridian Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States

12. IPD Sharing Statement

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Stem Cell Transplantation for Sickle Cell Anemia

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