Stem Cell Transplantation for Sickle Cell Anemia

NCT01877837 | Completed Phase 3 Results DMC

• 1 other identifier: Pro00001894
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

Stem cell transplant; Sickle cell; Stem cell transplantation; Related; Unrelated

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• Overall Survival

  2 years

Study Arms (1)

Related donor

EXPERIMENTAL

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

Drug: Alemtuzumab; Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cells

Interventions

Alemtuzumab 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

Also known as: Alemtuzumab (Campath)

Related donor

Fludarabine 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

Also known as: Fludarabine (Fludara)

Related donor

Melphalan 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.

Also known as: Melphalan (Alkeran)

Related donor

Stem Cells PROCEDURE

Infusion of Hematopoietic Stem Cells

Related donor

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient Eligibility
• \) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Alemtuzumab; fludarabine; fludarabine phosphate; Melphalan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Results Point of Contact

• Title: Elana Smilow
• Organization: Hackensack Meridian Health

Elana.Smilow@hmhn.org

5519965673

Study Officials

• Jennifer Krajewski, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 14, 2013
• Study Start: June 1, 2011
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: November 7, 2022
• Results First Posted: November 7, 2022

Record last verified: 2022-10

Locations

US (1)