Thymoglobulin to Prevent Acute Graft vs. Host Disease (GvHD) in Patients With Acute Lymphocytic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) Receiving a Stem Cell Transplant

NCT ID: NCT00088543

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2006-04-30

Brief Summary

This study involves the use of a drug called Thymoglobulin, which is approved in the USA to treat kidney transplant rejection and in Canada to treat and to prevent kidney transplant rejection. Thymoglobulin is not approved for the treatment or prophylaxis of graft versus host disease in bone marrow transplantation. This study is to evaluate two (2) doses of Thymoglobulin and its safety and effectiveness when used with a "myeloablative" conditioning regimen prior to receiving a stem cell transplant (also called bone marrow transplantation) from a matched, related donor.

A myeloablative regimen is typically composed of chemotherapy and radiation and destroys the subject's existing bone marrow.

Subjects meeting all inclusion and exclusion criteria and who have a relative with matching (genetically similar) stem cells who are also willing to donate them (i.e. matched-related-donor) are eligible to participate in this study. Following myeloablative therapy, the donor's cells are then transplanted (i.e. infused) into the subject's blood stream.

One of the most common complications of this type of transplant is graft-versus-host disease (GvHD). This is a condition where the transplanted donor cells attack the transplant recipient's body. Treatments, such as cyclosporine, are used to minimize the risk of GvHD following stem cell transplantation.

To enter this study, subjects must be having a matched-related donor stem cell transplant. If a subject qualifies for entry into this study, he/she will be assigned to receive Thymoglobulin at a dose of 4.5 mg/kg or 8.5 mg/kg. The treatment assignment is random and is not chosen by the subject or their physician.

Subjects are admitted to the hospital for the transplant procedure and are treated with Thymoglobulin over 3-5 days just prior to receiving the donor stem cells. The subject will also receive standard GvHD prophylaxis with cyclosporine. Methotrexate, which is commonly used by transplant centers to minimize the risk of GvHD, will not be used in this study.

Subjects will be monitored during treatment with Thymoglobulin and during the transplant hospitalization. Additional subject monitoring occurs at month 1, 100 days and 6 months following the transplant.

Approximately 60 study subjects from approximately 14 transplant centers in the United States and Canada will be enrolled.

Conditions

Acute Myelogenous Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Graft vs. Host Disease (GvHD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

1 Low dose

total dose 4.5 mg/kg Thymoglobulin

Group Type: EXPERIMENTAL

Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

Intervention Type: BIOLOGICAL

total dose 4.5 mg/kg

2 High dose

total dose 8.5 mg/kg Thymoglobulin

Group Type: EXPERIMENTAL

Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

Intervention Type: BIOLOGICAL

total dose 8.5 mg/kg

Interventions

Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

total dose 4.5 mg/kg

Intervention Type: BIOLOGICAL

Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

total dose 8.5 mg/kg

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Subject has an HLA-A, -B and -DRB1 identical related donor and must be fully matched at Class II. A high resolution molecular HLA typing (at least 4 digits) is mandatory for HLA Class II and optional for HLA Class I
• Subject has confirmed diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with acute myeloid leukemia (including secondary leukemia) in first complete remission (CR2) or acute lymphoid in CR1 or CR2.
• Subject is >= 18 and <= 55 years of age.
• Subject is receiving a myeloablative-conditioning regimen
• Men and women of childbearing age potential agree to practice an acceptable and reliable form of contraception during the study. Women must not be lactating or pregnant, and must have a negative serum pregnancy test.
• Subject has been fully informed and has signed an IRB-approved informed consent form.
• Subject is willing and able to follow study procedures for the 6 months post-transplant.
• The subject must be serologically negative for human immunodeficiency virus (HIV).
• Subject agrees to be followed for possible long-term safety outcomes for up to 12 months post-transplant.
• Subject has an ECOG performance score of 0-2.
• Subject has a creatinine of < 2.0mg/dL or creatinine clearance of > 50mL/min.
• Subject has an ejection fraction of >= 40%
• Subject has a serum bilirubin of < 2mg/dL.

Exclusion Criteria

• Subject is receiving fludarabine, a non-myeloablative regimen, or other purine analogues as part of the conditioning regimen.
• Subject is receiving an ex vivo engineered or processed graft (CD34+ enrichment, T-cell depletion, etc.)
• Subject has documented uncontrolled central nervous system (CNS) disease.
• Subject is expected to receive or has received methotrexate for GvHD prophylaxis.
• Subject has alanine aminotransferase (ALT)or aspartate aminotransferase (AST) level of > 3x the upper limit of normal range within 3 weeks prior to transplant.
• Subject has used any experimental agent within 30 days prior to the date of signing the informed consent.
• Subject is receiving or has received a bone marrow transplant from a donor who has positive serology for HIV, hepatitis B virus(HBV), hepatitis C virus (HCV) or syphilis.
• Subject has a known contraindication to administration of rabbit anti-thymocyte globulin.
• Subject is currently abusing drugs or alcohol or, in the opinion of the Investigator, is at high risk for poor compliance.
• Subject, who in the opinion of the Investigator, has significant medical or psychological problems that warrants exclusion. Examples of significant problems include, but are not limited to, morbid obesity or severe cardiac disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

University of Alabama-Birmingham Hospital

Birmingham, Alabama, United States

UCLA Medical Center

Los Angeles, California, United States

Shands at the University of Florida, Division of Hematology/Oncology

Gainesville, Florida, United States

Emory University Hospital

Atlanta, Georgia, United States

Massachusetts General Hospital Cox Bldg Room 640

Boston, Massachusetts, United States

Dana Farber Cancer Institute Dana 1B11

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center KS121

Brookline, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

The Nebraska Medical Center

Omaha, Nebraska, United States

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Princess Margaret Hospital, University Health Network

Toronto, Ontario, Canada

Countries

United States; Canada

Related Links

http://www.thymoglobulin.com/home/thymo_pdf_pi.pdf

US FDA Approved Full Prescribing Information for Thymoglobulin®

Other Identifiers

SMC-101-1026

Identifier Type: -

Identifier Source: org_study_id