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

March 4, 2015 updated by: Fred Hutchinson Cancer Center

A PHASE I/II STUDY OF RAPAMYCIN (SIROLIMUS) IN COMBINATION WITH METHOTREXATE (MTX) AND CYCLOSPORINE (CPS) IN PATIENTS UNDERGOING MARROW TRANSPLANTATION FROM RELATED DONORS MISMATCHED FOR ONE HLA ANTIGEN IN THE DIRECTION OF GRAFT-VERSUS-HOST DISEASE (GVHD)

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: H. Joachim Deeg, MD, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1996

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

September 1, 2004

First Posted (Estimate)

September 2, 2004

Study Record Updates

Last Update Posted (Estimate)

March 6, 2015

Last Update Submitted That Met QC Criteria

March 4, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1096.00
  • FHCRC-1096.00
  • NCI-H96-0928
  • CDR0000064855 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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