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

NCT00928018 | Completed Phase 3 Results DMC

• 2 other identifiers: 09-073CA142106
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 5

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.

Conditions

Non-hodgkin Lymphoma; Hodgkin Lymphoma

Keywords

allogeneic stem cell transplant; reduced intensity conditioning; graft versus host disease; GVHD; RIC transplantation

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (5)

• To Compare 2-year Progression-free Survival Between the Two Treatment Arms

  2 years

• To Compare the 2-year Cumulative Incidences of Disease Progression and of Non-relapse Mortality Between the Two Treatment Arms

  2 years

• To Compare the 180-day Cumulative Incidence of Grades II-IV and Grades III-IV Acute GVHD Between the Two Treatment Arms

  6 months

• To Compare the 2-year Cumulative Incidence of Chronic GVHD Between the Two Treatment Arms.

  2 years

• 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.

  2 years

Study Arms (2)

Sirolimus-Containing Regimen

ACTIVE COMPARATOR

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; Drug: Methotrexate; Drug: Tacrolimus

Sirolimus-Free regimen

ACTIVE COMPARATOR

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; Drug: Tacrolimus; Drug: Cyclosporine; Drug: MMF

Interventions

Sirolimus DRUG

Taken orally for at least 12 months

Also known as: Rapamycin

Sirolimus-Containing Regimen

Methotrexate DRUG

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

Also known as: Abbreviated MTX, Trade name:Trexall

Sirolimus-Containing Regimen; Sirolimus-Free regimen

Tacrolimus DRUG

Taken orally or given intravenously for at least 6 months

Also known as: Prograf

Sirolimus-Containing Regimen; Sirolimus-Free regimen

Cyclosporine DRUG

Taken orally or given intravenously for at least 6 months

Also known as: Brand names:, •Gengraf, •Neoral, •Sandimmune, •Sangcya

Sirolimus-Free regimen

MMF DRUG

Taken orally for about 2 months

Also known as: Mycophenolate mofetil (MMF), Brand Names:, CellCept, Myfortic

Sirolimus-Free regimen

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 26729448 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease; Graft vs Host Disease

Interventions

Sirolimus; Methotrexate; Tacrolimus; Cyclosporine; Cyclosporins; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Philippe Armand, MD, PhD
• Organization: Dana Farber Cancer Institute

parmand@partners.org

617-632-2305

Study Officials

• Philippe Armand, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 1, 2019
• Results First Posted: December 18, 2015

Record last verified: 2019-01

Locations

US (5)