Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

September 28, 2015 updated by: Swiss Group for Clinical Cancer Research

Master Protocol for Mantle Cell Lymphoma A Multicenter Phase II Trial Testing Everolimus (RAD001) for the Treatment of Patients With Relapsed or Therapy Resistant Mantle Cell Lymphoma

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with relapsed or refractory mantle cell lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Evaluation of the efficacy and tolerability of everolimus in patients with relapsed or therapy-resistant mantle cell lymphoma.

Secondary

  • Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
  • Investigation of immunoglobulin heavy chain variable gene somatic hypermutations (Ig-V_H) in classical mantle cell lymphoma as compared to blastoid mantle cell lymphoma, in particular in regard to their frequency, mutation distribution pattern (antigen selected vs. at random), and the individually involved Ig-V_H families.
  • Evaluation of a putative impact of Ig-V_H on clinical outcome.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bone marrow and peripheral blood samples are collected periodically and analyzed for molecular response by PCR. Molecular studies are also performed on DNA level formalin-fixed paraffin-embedded tissue samples.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Grenoble, France, 38043
        • CHU de Grenoble - Hopital de la Tronche
      • Pessac, France, 33604
        • Hôpital Haut Levêque
      • Tours, France, 37044
        • Centre Hospitalier Universitaire Bretonneau de Tours
      • Villejuif, France, F-94805
        • Institut Gustave Roussy
  • Italy
      • Bologna, Italy, 40138
        • University of Bologna Medical School
      • Milan, Italy, 20141
        • European Institute of Oncology
  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Hirslanden Klinik Aarau
      • Baden, Switzerland, CH-5404
        • Kantonsspital Baden
      • Basel, Switzerland, CH-4031
        • Universitaetsspital-Basel
      • Bellinzona, Switzerland, 6500
        • Istituto Oncologico della Svizzera Italiana
      • Bern, Switzerland, CH-3010
        • Inselspital Bern
      • Chur, Switzerland, CH-7000
        • Kantonsspital Graubuenden
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Olten, Switzerland, CH-4600
        • Kantonsspital Olten
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen
      • Thonex-Geneve, Switzerland, CH-1226
        • Hopitaux universitaires de Geneve
      • Winterthur, Switzerland, CH-8400
        • Kantonsspital Winterthur
      • Zurich, Switzerland, CH-8063
        • City Hospital Triemli
      • Zurich, Switzerland, CH-8091
        • Universitaetsspital Zuerich
      • Zurich, Switzerland, CH-8032
        • Klinik Hirslanden
      • Zurich, Switzerland, 8002
        • Onkozentrum - Klinik im Park

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Histologically or cytologically confirmed relapsed or chemotherapy/immunotherapy-resistant mantle cell lymphoma

    • No more than 3 lines of prior systemic treatment
  • At least one measurable lesion ≥ 15 mm in its greatest transverse diameter by CT scan

Exclusion criteria:

  • Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningosis)
  • Newly diagnosed mantle cell lymphoma
  • Patients suitable for intensive treatment (e.g., hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride and dexamethasone with high-dose methotrexate and cytarabine [HyperCVAD])

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • WHO performance status ≤ 2
  • Creatinine clearance ≥ 30mL/min
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • AST and ALT ≤ 2 times ULN
  • Neutrophils ≥ 1,500/mm³ (≥ 1,000/mm³ with marrow infiltration)
  • Thrombocytes ≥ 100,000/mm³ (≥ 75,000/mm³ in case of bone marrow infiltration)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after study participation

Exclusion criteria:

  • Prior or concurrent hematological malignancies

    • Patients with prior solid organ tumors that required no treatment over the last 5 years and are currently free of disease are eligible

  • Cardiovascular disease including any of the following:

    • NYHA class III or IV congestive heart failure
    • Unstable angina pectoris
    • Significant arrhythmia or arrhythmia requiring chronic treatment
    • Myocardial infarction in the last 3 months

  • Serious underlying medical condition which could impair the ability of the patient to participate in the trial including any of the following:

    • Uncontrolled diabetes mellitus
    • Gastric ulcers
    • Active autoimmune disease
    • Ongoing infection (e.g., HIV or hepatitis)

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

  • Prior radiation where the indicator lesion(s) are in the irradiated field
  • Prior organ transplantation
  • Participation in another clinical trial within 30 days prior to study entry
  • Concurrent anticancer drugs/treatments or experimental medications
  • Other concurrent investigational therapy
  • Other concurrent chemotherapy, immunotherapy, or radiotherapy (including palliative radiotherapy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: everolimus
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:
  • RAD001
Genetic: molecular response by PCR
Bone marrow and peripheral blood samples are collected periodically and analyzed for molecular response by PCR. Molecular studies are also performed on DNA level formalin-fixed paraffin-embedded tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Evaluation of the efficacy and tolerability of everolimus
Time Frame: Until treatment ends
Until treatment ends

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
Time Frame: Until treament ends
Until treament ends
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations
Time Frame: Until treatment ends
Investigation of immunoglobulin heavy chain variable gene somatic hypermutations (Ig-V_H) in classical mantle cell lymphoma as compared to blastoid mantle cell lymphoma, in particular in regard to their frequency, mutation distribution pattern (antigen selected vs. at random), and the individually involved Ig-V_H families.
Until treatment ends
Evaluation of a putative impact of Ig-V_H on clinical outcome.
Time Frame: Until treatment ends
Until treatment ends

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Principal Investigator: Christoph Renner, MD, Universitaetsspital Zuerich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

August 14, 2007

First Submitted That Met QC Criteria

August 14, 2007

First Posted (Estimate)

August 15, 2007

Study Record Updates

Last Update Posted (Estimate)

September 29, 2015

Last Update Submitted That Met QC Criteria

September 28, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 36/06
  • EU-20749
  • 2007-001108-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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