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 recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2006 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00093587
First received: October 6, 2004
Last updated: November 5, 2013
Last verified: January 2006
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: August 2004
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 18 to 55

Performance status

  • ECOG 0-3

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

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

Renal

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

Cardiovascular

  • Ejection fraction > 40%
  • No severe cardiac disease

Other

  • 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

PRIOR CONCURRENT THERAPY:

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)

Chemotherapy

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

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • 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
  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: NCT00093587

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1678
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Gary J. Schiller, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00093587     History of Changes
Other Study ID Numbers: CDR0000389241, UCLA-0402009-01, GENZ-SMC-101-1026
Study First Received: October 6, 2004
Last Updated: November 5, 2013
Health Authority: United States: Federal Government

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:
Graft vs Host Disease
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Enzyme Inhibitors
Antifungal Agents

ClinicalTrials.gov processed this record on July 23, 2014