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 - Article Cancer Chemotherapy
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.
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 |
Procedure: allogeneic bone marrow transplantation
Procedure: biological response modifier therapy
Procedure: bone marrow ablation with stem cell support
Procedure: bone marrow transplantation
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
- 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.
- 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.
Ages Eligible for Study: 18 Years - 55 Years, Genders Eligible for Study: Both
- 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
- ECOG 0-3
- 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
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)
- See Disease Characteristics
- No prior or concurrent methotrexate for graft-vs-host disease prophylaxis
- 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
Location and Contact Information
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, 90095-1678, United States; Recruiting
Gary John Schiller, MD, Principal Investigator, Jonsson Comprehensive Cancer Center
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
Cache Date: April 9, 2005