Tacrolimus/Sirolimus/Methotrexate Versus Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Information provided by (Responsible Party):
Philippe Armand, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00928018
First received: June 24, 2009
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

This trial is comparing whether using a drug called sirolimus for graft versus host disease (GVHD) prevention can decrease the chance of the participant's lymphoma relapsing after transplantation, compared to using a standard GVHD prevention regimen without sirolimus. Since mTOR inhibitors have anti-lymphoma activity, their use after transplantation may lead to a decreased risk of relapse and hence better transplantation outcome.


Condition Intervention Phase
Non-hodgkin Lymphoma
Hodgkin Lymphoma
Drug: Sirolimus
Drug: Methotrexate
Drug: Tacrolimus
Drug: Cyclosporine
Drug: MMF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Multicenter, Randomized Trial Comparing Tacrolimus/Sirolimus/Methotrexate Versus Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To compare the 2-year rate of overall survival of patients with lymphoma undergoing RIC SCT between those receiving Tacrolimus/Sirolimus/Methotrexate and those receiving Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the 2-year rate of progression-free survival between the two treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To compare the 2-year cumulative incidences of disease progression and of non-relapse mortality between the two treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To compare the 180-day cumulative incidence of grades 2-4 and grades 3-4 acute GVHD between the two treatment arms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To compare the 2-year cumulative incidence of chronic GVHD between the two treatment arms. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To compare the 2-year of overall survival, progression-free survival, cumulative incidences of progression and non-relapse mortality between the treatment arms for each histology studied. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: June 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sirolimus-Containing Regimen

The Sirolimus containing arm will consist of the following drugs:

Experimental Arm: tacrolimus + sirolimus + low-dose methotrexate

Tacrolimus: Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.

Sirolimus:Given as a loading oral dose of 12 mg on day -3, then as a daily maintenance dose of 4 mg starting on day -2.

Methotrexate: Administered by intravenous bolus infusion, per institutional standard, at a dose of 5 mg/m2 on days +1, +3 and +6.

Drug: Sirolimus
Taken orally for at least 12 months
Other Name: Rapamycin
Drug: Methotrexate
Given intravenously on the first, third and sixth day after transplant
Other Names:
  • Abbreviated MTX
  • Trade name:Trexall
Drug: Tacrolimus
Taken orally or given intravenously for at least 6 months
Other Name: Prograf
Active Comparator: Sirolimus-Free regimen

There are two choices for the Sirolimus free arm:

Control Arm 1: tacrolimus + methotrexate

Tacrolimus:Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.

Methotrexate:Administered by intravenous bolus infusion at a dose of 5 mg/m2 on days +1, +3 and +6. For patients receiving stem cells from unrelated donors, an additional dose will be given on day +11.

Control Arm 2: cyclosporine + MMF

Cyclosporine: administered orally at a dose of 6 mg/kg based on ABW bid starting on day -3.

MMF:administered at a dose of 3gm daily orally (or intravenously if the patient cannot tolerate oral administration) divided in 2 or 3 doses (bid or tid) depending on physician preference starting on day 3.

Drug: Methotrexate
Given intravenously on the first, third and sixth day after transplant
Other Names:
  • Abbreviated MTX
  • Trade name:Trexall
Drug: Tacrolimus
Taken orally or given intravenously for at least 6 months
Other Name: Prograf
Drug: Cyclosporine
Taken orally or given intravenously for at least 6 months
Other Names:
  • Brand names:
  • •Gengraf
  • •Neoral
  • •Sandimmune
  • •Sangcya
Drug: MMF
Taken orally for about 2 months
Other Names:
  • Mycophenolate mofetil (MMF)
  • Brand Names:
  • CellCept
  • Myfortic

Detailed Description:
  • Because no one knows which of the study options is best, participants will be "randomized" into one of the two possible groups for GVHD prophylaxis: 1) a sirolimus-containing regimen (tacrolimus, sirolimus and methotrexate) or 2) a sirolimus-free regimen (tacrolimus and methotrexate or cyclosporine and mycophenolate mofetil).
  • Participants will receive a reduced intensity conditioning regimen. This is done to prepare the body for transplantation. This will consist of a combination of drugs (either fludarabine and busulfan or fludarabine, cyclophosphamide and low-dose total body irradiation). The purpose of these drugs is to weaken the immune system and lower the chance of the body rejecting the donated stem cells.
  • Participants will also receive the GVHD prophylaxis regimen that they have been randomized to. These drugs will lower the chance of rejecting the donor cells and lower the chance of developing GVHD.
  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients will be eligible if their primary indication for transplantation is among the following: Indolent B-cell non-Hodgkin lymphoma (NHL); Aggressive B-Cell NHL; T-cell NHL; or Hodgkin Lymphoma.
  • Patients must have one of the following combinations of disease status and disease histology at the time of enrollment: 1) Patients may be transplanted as part of first-line therapy if they have one of the following histologies: CLL with adverse cytogenetics, MCL or, T-cell NHL. 2) Patients may be transplanted as part of treatment for relapsed or refractory disease without a prior autologous transplantation of they have one of the following histologies: Indolent NHL (including CLL/SLL), MCL or T-cell NHL. 3) Patients may be transplanted as part of treatment for disease that has relapsed or progressed after autologous transplantation if they have any of the histologies listed above. Patients may also be enrolled without a prior autologous transplantation if they have a contraindication to autologous transplantation, in the opinion of the treating clinician. 4) There is no minimal or maximal time interval from the patient's last anti-lymphoma therapy and the time of transplantation.
  • 18-72 years of age
  • Matched related or matched unrelated donor
  • Donor willing to donate peripheral blood stem cells and meeting institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells according to individual transplant center criteria.

Exclusion Criteria:

  • Patients with Burkitt lymphoma or DLBCL with a c-myc rearrangement
  • Karnofsky performance status of less than 70% at the time of registration
  • Prior allogeneic stem cell transplantation (note that prior autologous stem cell transplantation is allowed)
  • Uncontrolled infection
  • Serum creatinine 2.0mg/dl or greater
  • Total bilirubin 2.0mg/dl or greater (unless related to hemolysis or Gilbert's syndrome)
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times or greater than the institutional upper limit of normal
  • Left ventricular ejection fraction < 30%
  • Cholesterol > 500mg/dl or triglycerides > 500 mg/dl despite appropriate treatment
  • Seropositivity for HIV
  • Pregnancy or breast-feeding (effective contraception must be used during therapy and for at least 6 months after the end of immunosuppressive agents)
  • Prior history of allergy to sirolimus, tacrolimus, cyclosporine, methotrexate or MMF
  • Concomitant treatment with another investigational drug (unless cleared by study chair)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00928018

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Investigators
Principal Investigator: Philippe Armand, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00928018     History of Changes
Other Study ID Numbers: 09-073
Study First Received: June 24, 2009
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
allogeneic stem cell transplant
reduced intensity conditioning
graft versus host disease
GVHD
RIC transplantation

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Sirolimus
Mycophenolic Acid
Cyclosporine
Everolimus
Mycophenolate mofetil
Methotrexate
Tacrolimus
Cyclosporins
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on October 19, 2014