Clinical Trial: Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

This study is currently recruiting patients.

Sponsored by: Fred Hutchinson Cancer Research Center
Information provided by: National Cancer Institute (NCI)


RATIONALE: A peripheral blood stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Tacrolimus, mycophenolate mofetil, and sirolimus may stop this from happening.

PURPOSE: This randomized phase II trial is studying how well giving tacrolimus, mycophenolate mofetil, and sirolimus works compared to tacrolimus and mycophenolate mofetil alone in preventing acute graft-versus-host disease in patients who are undergoing donor stem cell transplant for hematologic cancer.

Condition Treatment or Intervention Phase
childhood Hodgkin's lymphoma
childhood non-Hodgkin's lymphoma
Graft Versus Host Disease
hematopoietic and lymphoid cancer
 Drug: fludarabine
 Drug: mycophenolate mofetil
 Drug: sirolimus
 Drug: tacrolimus
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: chemotherapy
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: peripheral blood stem cell transplantation
 Procedure: radiation therapy
 Procedure: supportive care/therapy
Phase II

MedlinePlus related topics:  Hodgkin's Disease;   Immune System and Disorders;   Lymphoma

Study Type: Interventional
Study Design: Treatment

Official Title: Phase II Randomized Study of Postgrafting Immunosuppression Comprising Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus to Prevent Acute Graft-Versus-Host Disease After Unrelated Donor Filgrastim (G-CSF)-Mobilized Peripheral Blood Mononuclear Cell Transplantation With Nonmyeloablative Conditioning in Patients With Hematologic Malignancies

Further Study Details: 



  • Compare the efficacy of these regimens in reducing the incidence of nonrelapse mortality from infections and GVHD before day 200 to ≤ 15% in these patients.
  • Compare the use of high-dose corticosteroids in patients treated with these regimens vs those treated on the following protocols: , , and .
  • Compare overall survival and progression-free survival of patients treated with these regimens vs those treated on FHCRC-1463.00, FHCRC-1641.00, and FHCRC-1668.00.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to transplant center (FHCRC vs other), number of prior chemotherapy treatments (0-2 vs ≥ 3), and age (under 55 vs 55 and over).

  • Conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -4 to -2 and low-dose total body irradiation (TBI) on day 0.
  • Allogeneic filgrastim (G-CSF)-mobilized peripheral blood mononuclear cell (G-PBMC) transplantation: After the completion of TBI, patients receive G-PBMCs on day 0.
  • Patients are randomized to 1 of 3 treatment arms.
  • Arm I: Beginning within 4-6 hours after G-PBMC infusion, patients receive oral mycophenolate mofetil (MMF) 3 times daily on days 0-29, and in the absence of graft-vs-host disease (GVHD), twice daily on days 30-96. MMF is tapered beginning on day 40 and continuing until day 96. Patients also receive oral tacrolimus twice daily on days -3 to 99 followed by a slow taper until day 180.
  • Arm II: Beginning within 4-6 hours after G-PBMC infusion, patients receive oral MMF 3 times daily on days 0-29, and in the absence of GVHD, twice daily on days 30-180. Patients also receive oral tacrolimus twice daily on days -3 to 100.
  • Arm III: Patients receive MMF and tacrolimus as in arm II. Patients also receive oral sirolimus once daily on days -3 to 80. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 5 years.

PROJECTED ACCRUAL: A total of 150 patients (50 per treatment arm) will be accrued for this study within 1.5 years.


Genders Eligible for Study:  Both



  • Diagnosis of a hematologic malignancy, including, but not limited to, the following:
  • Chronic lymphocytic leukemia and age ≤ 50 years, meeting one of the following criteria:
  • Refractory to fludarabine
  • Failed to achieve a complete response or partial response after therapy with a fludarabine-containing regimen (or another nucleoside analog [e.g., cladribine or pentostatin])
  • Disease relapse within 12 months after completing a fludarabine-containing regimen (or another nucleoside analog)
  • Aggressive non-Hodgkin's lymphoma (NHL), including, but not limited to, diffuse large B-cell NHL
  • Not eligible for autologous hematopoietic stem cell transplantation (HSCT) or conventional myeloablative HSCT or failed prior autologous HSCT
  • Mantle cell NHL in first complete remission (CR)
  • Low-grade NHL
  • < 6-month duration of CR between courses of conventional therapy
  • Hodgkin's lymphoma
  • Failed prior frontline therapy
  • Multiple myeloma
  • Must have received prior chemotherapy
  • Consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT allowed
  • Acute myeloid leukemia (AML)
  • < 5% marrow blasts
  • Acute lymphoblastic leukemia
  • < 5% marrow blasts
  • Chronic myelogenous leukemia (CML)
  • Chronic or accelerated phase
  • Prior autografts after high-dose therapy or prior intensive chemotherapy with filgrastim (G-CSF)-mobilized peripheral blood mononuclear cell autologous or conventional HSCT for advanced CML allowed provided patient is in chronic phase or CR and has < 5% marrow blasts
  • Myelodysplastic syndromes (MDS)
  • Refractory anemia (RA) or RA with ringed sideroblasts only
  • < 5% marrow blasts*
  • Myeloproliferative disease (MPD)
  • < 5% marrow blasts* NOTE: *Patients with MDS or MPD with > 5% marrow blasts (including those with transformation to AML) must have received prior cytotoxic chemotherapy
  • Meets one of the following criteria:
  • Treatable by unrelated HSCT and age > 50 years
  • Treatable by allogeneic HSCT and age ≤ 50 years, meeting one of the following criteria:
  • Considered high risk for regimen-related toxicity associated with a conventional transplant (> 40% risk of transplant-related mortality) due to pre-existing medical conditions or prior therapy
  • Charleston comorbidity index score ≥ 1 allowed
  • Refused conventional HSCT
  • No rapidly progressive intermediate- or high-grade NHL
  • No CNS involvement with disease refractory to intrathecal chemotherapy
  • No nonhematologic tumors
  • Must have an unrelated donor available meeting the following criteria:
  • Matched for HLA-A, -B, -C, -DRB1, and -DQB1 by high-resolution typing
  • Only a single allele disparity allowed for HLA-A, -B, or -C by high-resolution typing
  • Homozygosity at a mismatched allele in the graft rejection vector is considered a two-allele mismatch
  • Negative anti-donor cytotoxic crossmatch NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.


  • See Disease Characteristics
  • Any age

Performance status

  • Karnofsky 60-100%

Life expectancy

  • Not specified


  • See Disease Characteristics



  • Not specified


  • Ejection fraction ≥ 35%
  • Required if prior anthracycline exposure or history of cardiac disease
  • No hypertension > grade 2


  • DLCO ≥ 40%
  • No supplementary continuous oxygen
  • Pulmonary nodules allowed at discretion of principal investigator


  • HIV negative
  • No fungal infection with radiological progression after treatment with amphotericin B or active triazole for > 1 month
  • No active bacterial or fungal infections that are unresponsive to medical therapy
  • Not pregnant
  • Fertile patients must use effective contraception during and for 1 year after study treatment


  • See Disease Characteristics
  • Prior cytokines or rituximab for cytoreduction allowed
  • No concurrent conventional allogeneic HSCT


  • See Disease Characteristics
  • More than 3 weeks since prior cytotoxic agents for cytoreduction except hydroxyurea, low-dose cytarabine, or chlorambucil
  • No concurrent conventional chemotherapy

Endocrine therapy

  • Not specified


  • No other concurrent radiotherapy


  • Not specified


Location and Contact Information

      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
Karl Georg Blume, MD  650-723-0822 

      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  United States; Recruiting
Peter McSweeney, MD  303-388-4876 

      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Amelia Langston, MD  404-778-1900 

      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Richard Maziarz, MD  503-494-4606 

      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
Michael A. Pulsipher, MD  801-585-0303 

      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
Michael B. Maris, MD  206-667-2480 

      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
Christopher Bredeson, FRCPC, MD, MSC  414-456-8325 

      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
Lars Vindelov, MD  45-3545-1145 

      Medizinische Universitaetsklinik I, Cologne,  D-50924,  Germany; Recruiting
Kai Huebel, MD  49-221-478-5133 

      Universitaet Leipzig, Leipzig,  D-04103,  Germany; Recruiting
Dietger Niederwieser, MD  49-341-971-3050 

      Universitaetsklinikum Tuebingen, Tuebingen,  D-72076,  Germany; Recruiting
Wolfgang Bethge, MD  49-4707-1298-2711 

      Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino, Turin,  10126,  Italy; Recruiting
Benedetto Bruno, MD, PhD  39-011-633-9064 

Study chairs or principal investigators

Michael B. Maris, MD,  Principal Investigator,  Fred Hutchinson Cancer Research Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000407783; FHCRC-1938.00; NCT00105001
Record last reviewed:  February 2005
Last Updated:  March 15, 2005
Record first received:  March 3, 2005 Identifier:  NCT00105001
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005