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

This study is currently recruiting patients.

Sponsors and Collaborators: Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Antithymocyte globulin and cyclosporine may prevent 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 transplantation for acute lymphoblastic leukemia or acute myeloid leukemia.

Condition Treatment or Intervention
adult acute lymphoblastic leukemia
adult acute myeloid leukemia
Graft Versus Host Disease
secondary acute myeloid leukemia
 Drug: anti-thymocyte globulin
 Drug: busulfan
 Drug: cyclophosphamide
 Drug: cyclosporine
 Procedure: allogeneic bone marrow transplantation
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: bone marrow transplantation
 Procedure: chemotherapy
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: peripheral blood stem cell transplantation
 Procedure: radiation therapy
 Procedure: supportive care/therapy

MedlinePlus related topics:  Bone Marrow Diseases;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood;   Lymphatic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Pilot Randomized Study of Anti-Thymocyte Globulin and Cyclosporine for the Prevention of Acute Graft-Versus-Host Disease in Patients With Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia Receiving a Myeloablative Conditioning Regimen Comprising Cyclophosphamide With or Without Radiotherapy Followed By HLA-Identical Matched Related Allogeneic Stem Cell Transplantation

Further Study Details: 

OBJECTIVES: Primary

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.
  • 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   -   55 Years,  Genders Eligible for Study:  Both

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

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

Location and Contact Information


California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States; Recruiting
Gary John Schiller, MD  310-825-5513    garyjs@ucla.edu 

Study chairs or principal investigators

Gary John Schiller, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000389241; UCLA-0402009-01; GENZ-SMC-101-1026; NCT00093587
Record last reviewed:  September 2004
Last Updated:  January 7, 2005
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093587
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005