Stem Cell Transplantation for Sickle Cell Anemia

NCT ID: NCT01877837

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2021-09-30

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

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Related donor

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

Group Type: EXPERIMENTAL

Alemtuzumab

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

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.

Stem Cells

Intervention Type: PROCEDURE

Infusion of Hematopoietic Stem Cells

Interventions

Alemtuzumab

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

Fludarabine

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

Melphalan

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: DRUG

Stem Cells

Infusion of Hematopoietic Stem Cells

Intervention Type: PROCEDURE

Other Intervention Names

Alemtuzumab (Campath); Fludarabine (Fludara); Melphalan (Alkeran)

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)

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hackensack Meridian Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Krajewski, MD

Role: PRINCIPAL_INVESTIGATOR

Hackensack Meridian Health

Locations

Hackensack University Medical Center

Hackensack, New Jersey, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00001894

Identifier Type: -

Identifier Source: org_study_id