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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00088543
First received: July 29, 2004
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention
Acute Myelogenous Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Graft vs. Host Disease (GvHD)
Biological: Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Pilot Trial of Two Dose Levels of Thymoglobulin as Part of a Myeloablative-Conditioning for a Human Leukocyte Antigen (HLA) Identical Matched Related Donor (MRD) Stem Cell Transplant (SCT) With Cyclosporine (CSa) as Post-transplant Graft vs. Host Disease (GvHD) Prophylaxis

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Incidence of Grade II to IV acute GvHD in the first 100 days after transplant. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of treatment related adverse events and serious adverse events at 100 days and 6 months post transplant [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]
  • Patient survival at 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]
  • transplant related mortality at 100 days or 6 months after transplant [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]
  • severity and outcomes of acute GvHD [ Time Frame: 100 days & 6 mos ] [ Designated as safety issue: Yes ]
  • any events of infection at 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]
  • incidence (or absence) of mucositis [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • how many days in the first month after transplant certain types of narcotics are used to reduce pain [ Time Frame: 30days ] [ Designated as safety issue: Yes ]
  • whether the subject's blood counts after transplant reach a stable level and how quickly [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
  • incidence of re-hospitalization in the first 6 months after transplant [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • any recurrence of the subject's leukemic disease, and how long the subject was able to stay in remission [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
  • incidence and severity of chronic GvHD, and the extent, after 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]
  • Disease free survival [ Time Frame: 100 days and 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: March 2004
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Low dose
total dose 4.5 mg/kg Thymoglobulin
Biological: Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]
total dose 4.5 mg/kg
Experimental: 2 High dose
total dose 8.5 mg/kg Thymoglobulin
Biological: Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]
total dose 8.5 mg/kg

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088543

Locations
United States, Alabama
University of Alabama-Birmingham Hospital
Birmingham, Alabama, United States, 35249
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Florida
Shands at the University of Florida, Division of Hematology/Oncology
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute Dana 1B11
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cox Bldg Room 640
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center KS121
Brookline, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
The Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Canada, Ontario
Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital, University Health Network
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
No publications provided

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00088543     History of Changes
Other Study ID Numbers: SMC-101-1026
Study First Received: July 29, 2004
Last Updated: August 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Genzyme, a Sanofi Company:
Acute myelogenous leukemia (AML)
Acute lymphocytic leukemia (ALL)
Anti-T cell antibodies
Allogenic stem cell transplant
Graft vs. Host Disease (GvHD)

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Graft vs Host Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 19, 2014