Reduced Intensity Transplant Conditioning Regimen for Severe Thalassemia

NCT01005576 | Completed Phase 2 Results DMC

• 1 other identifier: TCRN-NMD 0901
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 18

Brief Summary

This study is being done to determine if blood cell transplants, with either bone marrow or cord blood from unrelated donors, are effective in children with severe thalassemia and if this treatment approach has acceptable risks and side effects. This study includes a preparative regimen with Hydroxyurea, Alemtuzumab, Fludarabine, Thiotepa and Melphalan that provides intense host immunosuppression without myeloablation. The primary hypothesis is that this regimen will promote stable engraftment of unrelated donor hematopoietic cells, support normal erythropoiesis, and result in an event free survival of \> 75% of children with thalassemia major.

Conditions

Severe Thalassemia

Keywords

Thalassemia; Alemtuzumab; Hematopoietic cell transplant; non-myeloablative

Outcome Measures

Primary Outcomes (1)

• Primary Objective: Event-free Survival at 1 Year.

  1 year

Secondary Outcomes (4)

• Development of Graft Versus Host Disease (GVHD)

  2 years

• Median Time to ANC Engraftment

  100 days

• Median Time to Platelet Engraftment

  100 days

• Incidence of Disease Recurrence

  2 years

Study Arms (1)

Conditioning regimen

EXPERIMENTAL

Hydroxyurea days -50 to -21 Alemtuzumab days -21 to -19 Fludarabine days -8 to -4 Thiotepa day -4 Melphalan day -3 Stem cell infusion day 0

Drug: Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan

Interventions

Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan DRUG

Days -50 to -21: Hydroxyurea 30mg/kg po Day -22: Alemtuzumab 3mg IV Day -21: Alemtuzumab 10mg IV Day -20: Alemtuzumab 15mg IV Day -19: Alemtuzumab 20mg IV Day -8: Fludarabine 30mg/m2 IV Day -7: Fludarabine 30mg/m2 IV Day -6: Fludarabine 30mg/m2 IV Day -5: Fludarabine 30mg/m2 IV Day -4: Fludarabine 30mg/m2 IV Day -4: Thiotepa 8mg/kg IV Day -3: Melphalan 140mg/m2 IV Day 0: Stem cell infusion

Conditioning regimen

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• years old
• Have transfusion dependent thalassemia major
• Shall not have an HLA-matched family donor
• Must have a suitably matched unrelated marrow donor or UCB product
• Lansky score \>/= 70
• Adequate pulmonary, renal, liver, and other organ function as defined in protocol
• Negative pregnancy test
• Adequate total nucleated cell or CD34+ dose of product as defined in protocol
• Iron chelation must be discontinued \>/= 48 hours prior to conditioning regimen

You may not qualify if:

• Pregnant or breastfeeding
• HIV positive
• Prior allogeneic marrow or stem cell transplantation

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Carelon Research: collaborator
• Pediatric Blood and Marrow Transplant Consortium: collaborator

Study Sites (18)

Regents of University of California- UCLA

Los Angeles, California, 90095, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

All Children's Research Institute, Inc.

St. Petersburg, Florida, 33701, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

The Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Methodist Healthcare System of San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Thalassemia

Interventions

fludarabine; 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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Shalini Shenoy
• Organization: Washington University School of Medicine

shalinishenoy@wustl.edu

314-454-6018

Study Officials

• Shalini Shenoy, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: November 2, 2009
• Study Start: January 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 13, 2017
• Results First Posted: October 20, 2017

Record last verified: 2017-11

Locations

US (18)