Antithymocyte Globulin and Cyclosporine in Preventing Graft-Versus-Host Disease in Patients Undergoing Chemotherapy With or Without Radiation Therapy Followed By Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

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: NCT00093587
Recruitment Status : Unknown
Verified January 2006 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : October 8, 2004
Last Update Posted : November 6, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine after transplant may stop this from happening.

PURPOSE: This randomized clinical trial is studying how well giving antithymocyte globulin together with cyclosporine works in preventing graft-versus-host disease in patients who are undergoing chemotherapy with or without radiation therapy followed by donor stem cell transplant for acute lymphoblastic leukemia or acute myeloid leukemia.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Leukemia Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Not Applicable

Detailed Description:



  • Compare the incidence of acute graft-vs-host disease (GVHD) within the first 100 days after transplantation in patients with acute lymphoblastic leukemia or acute myeloid leukemia treated with a myeloablative conditioning regimen comprising cyclophosphamide (with or without radiotherapy) and low- vs high-dose anti-thymocyte globulin followed by allogeneic HLA-matched related stem cell transplantation and cyclosporine.
  • Compare the incidence of serious adverse events within the first 100 days after transplantation in patients treated with these regimens.


  • Compare 100-day and 6-month survival in patients treated with these regimens.
  • Compare the severity of acute GVHD in patients treated with these regimens.
  • Compare the incidence of culture-proven infections at 100 days and 6 months after transplantation in patients treated with these regimens.
  • Compare the incidence of mucositis, in terms of presence, severity, and duration, in patients treated with these regimens.
  • Compare the number of days on opiate drugs within the first 30 days after transplantation in patients treated with these regimens.
  • Compare the time to engraftment in patients treated with these regimens.
  • Compare the incidence of hospitalization within the first 6 months after transplantation, in terms of length of initial stay, cumulative total days, and number of hospitalizations, in patients treated with these regimens.
  • Compare the relapse rate and time to relapse in patients treated with these regimens.
  • Compare the incidence and severity of chronic GVHD between 100 days and 6 months after transplantation in patients treated with these regimens.

OUTLINE: This is a pilot, randomized, open-label, multicenter study.

  • Conditioning: All patients receive a standard myeloablative-conditioning regimen that contains cyclophosphamide IV over 2 hours per center regimen, typically on days -6 to -3. Patients also undergo total body irradiation OR receive busulfan.
  • Graft-versus-host disease (GVHD) prophylaxis (as part of conditioning): Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive low-dose anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
    • Arm II: Patients receive high-dose anti-thymocyte globulin IV over 4-8 hours on days -5 to -1.
  • Allogeneic hematopoietic stem cell transplantation: Patients in both arms undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
  • Post-transplantation GVHD prophylaxis: Patients in both arms receive cyclosporine IV over 1-4 hours or orally twice daily beginning on day -1 and continuing until approximately day 60 followed by tapering doses until day 180 in the absence of GVHD.

Patients are followed at 7, 14, 21, 30, 100, and 180 days.

PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per treatment arm) will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Pilot Trial of Two Dose Levels of Thymoglobulin® as Part of a Myeloablative-Conditioning for a HLA Identical Matched Related Donor (MRD) Stem Cell Transplant With Cyclosporine (CsA) as Posttransplant Graft vs Host Disease (GvHD) Prophylaxis
Study Start Date : August 2004

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


  • Confirmed diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia

    • In first complete remission or second complete remission
  • Secondary AML allowed
  • HLA-A, -B, and -DRB1 identical related donor available AND must be fully matched at Class II by high-resolution molecular HLA typing (at least 4 digits)
  • Currently receiving a myeloablative conditioning regimen that includes cyclophosphamide

    • All patients from a center should receive the same conditioning regimen throughout the study
    • No fludarabine or other purine analogues (e.g. cladribine or pentostatin) as part of conditioning regimen
  • No uncontrolled CNS disease



  • 18 to 55

Performance status

  • ECOG 0-3

Life expectancy

  • Not specified


  • Not specified


  • Bilirubin < 2 mg/dL
  • ALT and/or AST ≤ 3 times normal


  • Creatinine < 2.0 mg/dL OR
  • Creatinine clearance > 50 mL/min


  • Ejection fraction > 40%
  • No severe cardiac disease


  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known contraindication to administration of rabbit anti-thymocyte globulin
  • No current drug or alcohol abuse
  • No significant medical or psychosocial problem or unstable disease state (including, but not limited to, morbid obesity) that would preclude study participation


Biologic therapy

  • No prior or concurrent bone marrow transplantation from a donor who has positive serology for HIV, hepatitis B virus, hepatitis C virus, or syphilis
  • No IV immunoglobulin prior to engraftment
  • No concurrent ex vivo engineered or processed graft (CD34+ enrichment or T-cell depletion)


  • See Disease Characteristics
  • No prior or concurrent methotrexate for graft-vs-host disease prophylaxis

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • More than 30 days since prior experimental agents
  • No other concurrent investigational agents

    • Enrollment in investigational studies (i.e., anti-microbial agents) allowed only for life threatening events or after exhausting other treatment modalities

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): NCT00093587

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1678
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Gary J. Schiller, MD Jonsson Comprehensive Cancer Center Identifier: NCT00093587     History of Changes
Other Study ID Numbers: CDR0000389241
First Posted: October 8, 2004    Key Record Dates
Last Update Posted: November 6, 2013
Last Verified: January 2006

Keywords provided by National Cancer Institute (NCI):
graft versus host disease
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Graft vs Host Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents