Clinical trial NCT00928018: Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-hodgkin Lymphoma
Hodgkin Lymphoma
Keywords: allogeneic stem cell transplant
reduced intensity conditioning
graft versus host disease
GVHD
RIC transplantation
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: National Cancer Institute (NCI)
First posted: 2009-06-25
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: To Compare 2-year Overall Survival of Patients With Lymphoma Undergoing RIC SCT Between Those Receiving Tacrolimus/Sirolimus/Methotrexate and Those Receiving Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil
timeFrame: 2 years
Secondary outcomes:
measure: To Compare 2-year Progression-free Survival Between the Two Treatment Arms
timeFrame: 2 years
measure: To Compare the 2-year Cumulative Incidences of Disease Progression and of Non-relapse Mortality Between the Two Treatment Arms
timeFrame: 2 years
measure: To Compare the 180-day Cumulative Incidence of Grades II-IV and Grades III-IV Acute GVHD Between the Two Treatment Arms
timeFrame: 6 months
measure: To Compare the 2-year Cumulative Incidence of Chronic GVHD Between the Two Treatment Arms.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Philippe Armand, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.