RATIONALE: Antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known which antibody therapy regimen is more effective for graft-versus-host disease. PURPOSE: Randomized phase II/III trial to compare the effectiveness of two different antibody therapy regimens in treating patients who have graft-versus-host disease that does not respond to steroid therapy.

Condition	Treatment or Intervention	Phase
Leukemia Testicular Cancer ovarian epithelial cancer Lymphoma Breast Cancer Multiple Myeloma kidney tumor	Procedure: supportive care  Procedure: biological response modifier therapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: non-specific immune-modulator therapy  Procedure: monoclonal antibody therapy  Behavior: supportive care/therapy  Procedure: antibody therapy  Drug: anti-thymocyte globulin  Drug: monoclonal antibody ABX-CBL	Phase II Phase III

Further Study Details: 

OBJECTIVES: I. Compare the 180 day survival and overall survival of patients with steroid resistant acute graft-versus-host disease (GVHD) treated with ABX-CBL versus anti-thymocyte globulin. II. Compare the efficacy of these drugs in this patient population. III. Compare the safety of these drugs in this patient population. IV. Compare the long term endpoints, such as the development of new malignancies, the onset of serious infections, or chronic GVHD, in patients treated with these drugs. V. Determine the toxicity of ABX-CBL in these patients.

PROTOCOL OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to International Bone Marrow Transplant Registry severity index (index B or C vs index D). Patients are randomized to one of two treatment arms. Arm I: Patients receive ABX-CBL IV over 2 hours on days 1-14. Treatment continues as twice weekly infusions for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive anti-thymocyte globulin IV on days 3, 5, 7, 9, 11, and 13. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 100 days, monthly for at least 3 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 92 patients (46 per arm) will be accrued for this study within 12-15 months.

Ages Eligible for Study:  1 Year and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of steroid resistant acute graft-versus-host disease (GVHD) with an International Bone Marrow Transplant Registry severity index of B, C, or D

• No chronic GVHD

Receiving high-dose steroids, such as prednisone, since diagnosis of acute GVHD and for no more than 14 total days

• No changes to prophylactic regimen for acute GVHD within the past 72 hours except for changes to maintain proper serum levels, or changes due to toxicity

Recipient of a single allogeneic bone marrow, peripheral blood stem cell, or cord blood transplant from any donor type within the past 68 days

• No second stem cell transplantation or subsequent donor cell product transplantation prior to and during study

--Prior/Concurrent Therapy--

Biologic therapy:

• See Disease Characteristics
• No prior murine product (exposure of donor cells to a murine product allowed)
• At least 5 days since prior anti-thymocyte globulin after stem cell transplantation

Chemotherapy: Not specified

Endocrine therapy:

• See Disease Characteristics
• Prior steroids for immunosuppression allowed
• No other prior immunosuppressants

Radiotherapy: Not specified

Surgery: Not specified

Other:

• At least 30 days since prior investigational agents*
• No other concurrent investigational agents*

[Note: *Investigational antifungals allowed]

--Patient Characteristics--

Age: 1 and over

Performance status: Not specified

Life expectancy: Not specified

Hematopoietic: Not specified

Hepatic: See Cardiovascular

Renal:

• Creatinine no greater than 2.5 times upper limit of normal OR
• No requirement of renal dialysis

Cardiovascular: No severe veno-occlusive disease exhibiting at least 2 of the following:

• Right upper quadrant tenderness
• Weight gain of 5% or more since initiation of conditioning regimen together with ascites
• Bilirubin greater than 12 mg/dL

Pulmonary:

• No need to maintain an 02 saturation greater than 90% with an FIO2 of greater than 50% OR
• No need for ventilator support

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after study
• HIV negative
• No history of alcohol or substance abuse
• No medical, psychiatric, or laboratory abnormality that would preclude study
• No multi-organ system failure
• No active systemic infection associated with greater than 60% short-term mortality such as: *Invasive mold infections (e.g., aspergillus or rhizopus) *Any lower respiratory tract infection caused by respiratory syncytial virus or parainfluenza *Any invasive infection with no approved therapy

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

Study chairs or principal investigators

Mary Carol Territo,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068482; UCLA-9911052; NCI-G01-1916; ABX-CB-9906
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012077
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08