Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Supportive care Closed 13 and over NCI FHCRC-1096.00 NCI-H96-0928, NCT00002790

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.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Prior/Concurrent Therapy:

At least 1 week since any investigational drug

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

General Eligibility Criteria:

--Population Characteristics--

Patients with any of the following hematologic disorders:
  Hematologic malignancy, including chronic myelogenous leukemia in
  chronic phase with an HLA-DR mismatch only donor available
  Myelodysplastic syndrome
  Aplastic anemia

Eligible for bone marrow transplantation per protocols FHCRC-697.0,
FHCRC-179.2, or FHCRC-174.2

Available donor who is a haplo-identical family member mismatched
for 1 HLA-A, -B, or -DRB1 locus in the GVH vector on the nonshared haplotype

--Prior/Concurrent Therapy--

At least 1 week since any investigational drug

--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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

H. Joachim Deeg, MD, Protocol chair		Ph: 206-667-5985 Email: jdeeg@fhcrc.org

Registry Information
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)
Trial Start Date		1996-03-13
Registered in ClinicalTrials.gov		NCT00002790
Date Submitted to PDQ		1996-03-13
Information Last Verified		2007-07-11
NCI Grant/Contract Number		CA18029

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