Prevention of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Receiving a Bone Marrow Transplant

NCT ID: NCT00002790

Last Updated: 2015-03-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-03-31

Brief Summary

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment with sirolimus, methotrexate, and cyclosporine may prevent this from happening.

PURPOSE: Phase I/II trial to study the effectiveness of sirolimus plus methotrexate and cyclosporine in preventing graft-versus-host disease in patients with hematologic malignancies who are receiving a bone marrow transplant.

Detailed Description

OBJECTIVES: I. Estimate the maximum tolerated dose of rapamycin that can be safely combined with standard methotrexate/cyclosporine prophylaxis for graft-versus-host disease (GVHD) in patients with hematologic disorders who have received a bone marrow transplant from a related donor who is mismatched for 1 HLA-A, -B, or -DR antigen in the GVHD direction.

OUTLINE: This is a dose escalation study. Groups of 6-12 patients receive escalating doses of rapamycin until the maximum tolerated dose of rapamycin given in combination with methotrexate/cyclosporine is determined. All patients receive cyclosporine from the day prior to transplant until day 50 post-transplant; the dose is then tapered over 130 days. Methotrexate is given on days 1, 3, and 6 post-transplant. Rapamycin is given every other day, days 7-59. Bone marrow transplantation occurs on day 0. Patients may not receive concurrent therapy with agents that could interfere with rapamycin metabolism, intravenous lipids, FK506 or other immunosuppressive agents (prednisone allowed), NSAIDs, or other cytotoxic agents. Patients are followed at 6 months for 2 years, then annually.

PROJECTED ACCRUAL: 12-36 patients will be accrued over 1-2.5 years.

Conditions

Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes

Study Design

• Primary Study Purpose: SUPPORTIVE_CARE

Interventions

cyclosporine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

sirolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: See General Eligibility Criteria

PATIENT CHARACTERISTICS: Age: 13 and over Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No cardiac disease No clinically significant cardiac abnormality No ischemia No recent injury on EKG Other: No intolerance or unresponsiveness to rapamycin No hypersensitivity to macrolide antibiotics, e.g., erythromycin, azithromycin, clarithromycin No requirement for medications that may significantly affect rapamycin metabolism, i.e.: Carbamazepine Ketoconazole Primidone Cimetidine Nicardipine Rifampin Diltiazem Phenobarbital Valproic acid Erythromycin Phenytoin Verapamil No uncontrolled systemic infection No pregnant or nursing women Negative pregnancy test required of fertile women Effective contraception required of fertile patients during and for 3 months after study Able to tolerate less than 400 mL of liquid oral intake

PRIOR CONCURRENT THERAPY: At least 1 week since any investigational drug

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

H. Joachim Deeg, MD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Other Identifiers

FHCRC-1096.00

Identifier Type: -

Identifier Source: secondary_id

NCI-H96-0928

Identifier Type: -

Identifier Source: secondary_id

CDR0000064855

Identifier Type: REGISTRY

Identifier Source: secondary_id

1096.00

Identifier Type: -

Identifier Source: org_study_id