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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00002790
First received: November 1, 1999
Last updated: May 10, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Leukemia
Myelodysplastic Syndromes
Drug: cyclosporine
Drug: methotrexate
Drug: sirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Supportive Care
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Estimated Enrollment: 36
Study Start Date: March 1996
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002790

Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: H. Joachim Deeg, MD Fred Hutchinson Cancer Research Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002790     History of Changes
Other Study ID Numbers: 1096.00, FHCRC-1096.00, NCI-H96-0928, CDR0000064855
Study First Received: November 1, 1999
Last Updated: May 10, 2011
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
childhood acute lymphoblastic leukemia
chronic lymphocytic leukemia
adult acute lymphoblastic leukemia
adult acute myeloid leukemia
chronic myelogenous leukemia
childhood acute myeloid leukemia/other myeloid malignancies
myelodysplastic syndromes
graft versus host disease
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Site
Cyclosporins
Cyclosporine
Methotrexate
Sirolimus
Everolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents

ClinicalTrials.gov processed this record on April 17, 2014