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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00088543
Recruitment Status : Completed
First Posted : July 30, 2004
Last Update Posted : March 18, 2015
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Graft vs. Host Disease (GvHD) Biological: Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)] Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : March 2004
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Incidence of Grade II to IV acute GvHD in the first 100 days after transplant. [ Time Frame: 100 days ]

Secondary Outcome Measures :
  1. 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 ]
  2. Patient survival at 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ]
  3. transplant related mortality at 100 days or 6 months after transplant [ Time Frame: 100 days and 6 months ]
  4. severity and outcomes of acute GvHD [ Time Frame: 100 days & 6 mos ]
  5. any events of infection at 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ]
  6. incidence (or absence) of mucositis [ Time Frame: continuous ]
  7. how many days in the first month after transplant certain types of narcotics are used to reduce pain [ Time Frame: 30days ]
  8. whether the subject's blood counts after transplant reach a stable level and how quickly [ Time Frame: Continuous ]
  9. incidence of re-hospitalization in the first 6 months after transplant [ Time Frame: 6 months ]
  10. any recurrence of the subject's leukemic disease, and how long the subject was able to stay in remission [ Time Frame: Continuous ]
  11. incidence and severity of chronic GvHD, and the extent, after 100 days and 6 months after transplant [ Time Frame: 100 days and 6 months ]
  12. Disease free survival [ Time Frame: 100 days and 6 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00088543

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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
Massachusetts General Hospital Cox Bldg Room 640
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Dana 1B11
Boston, Massachusetts, United States, 02115
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
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Study Director: Medical Monitor Genzyme, a Sanofi Company
Additional Information:
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Responsible Party: Genzyme, a Sanofi Company Identifier: NCT00088543    
Other Study ID Numbers: SMC-101-1026
First Posted: July 30, 2004    Key Record Dates
Last Update Posted: March 18, 2015
Last Verified: March 2015
Keywords provided by Sanofi ( 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:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Graft vs Host Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents