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

NCT ID: NCT00928018

Last Updated: 2019-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2014-11-30

Brief Summary

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.

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.

Conditions

Non-hodgkin Lymphoma; Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Sirolimus

Intervention Type: DRUG

Taken orally for at least 12 months

Methotrexate

Intervention Type: DRUG

Given intravenously on the first, third and sixth day after transplant

Tacrolimus

Intervention Type: DRUG

Taken orally or given intravenously for at least 6 months

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.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Given intravenously on the first, third and sixth day after transplant

Tacrolimus

Intervention Type: DRUG

Taken orally or given intravenously for at least 6 months

Cyclosporine

Intervention Type: DRUG

Taken orally or given intravenously for at least 6 months

MMF

Intervention Type: DRUG

Taken orally for about 2 months

Interventions

Sirolimus

Taken orally for at least 12 months

Intervention Type: DRUG

Methotrexate

Given intravenously on the first, third and sixth day after transplant

Intervention Type: DRUG

Tacrolimus

Taken orally or given intravenously for at least 6 months

Intervention Type: DRUG

Cyclosporine

Taken orally or given intravenously for at least 6 months

Intervention Type: DRUG

MMF

Taken orally for about 2 months

Intervention Type: DRUG

Other Intervention Names

Rapamycin; Abbreviated MTX; Trade name:Trexall; Prograf; Brand names: •Gengraf; •Neoral; •Sandimmune; •Sangcya; Mycophenolate mofetil (MMF); Brand Names: CellCept; Myfortic

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Philippe Armand, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philippe Armand, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Emory University Hospital

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Ohio State University

Columbus, Ohio, United States

Countries

United States

References

Armand P, Kim HT, Sainvil MM, Lange PB, Giardino AA, Bachanova V, Devine SM, Waller EK, Jagirdar N, Herrera AF, Cutler C, Ho VT, Koreth J, Alyea EP, McAfee SL, Soiffer RJ, Chen YB, Antin JH. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial. Br J Haematol. 2016 Apr;173(1):96-104. doi: 10.1111/bjh.13931. Epub 2016 Jan 5.

Reference Type: DERIVED

PMID: 26729448 (View on PubMed)

Other Identifiers

CA142106

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

09-073

Identifier Type: -

Identifier Source: org_study_id