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)


Phase 1/Phase 2
13 Years
N/A
Not Enrolling
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes

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Trial Information

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)


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.

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Supportive Care

Principal Investigator

H. Joachim Deeg, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1096.00

NCT ID:

NCT00002790

Start Date:

March 1996

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • 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
  • Graft vs Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

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