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
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Grenoble, France, 38043
- CHU de Grenoble - Hopital de la Tronche
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Pessac, France, 33604
- Hôpital Haut Lévêque
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Tours, France, 37044
- Centre Hospitalier Universitaire Bretonneau de Tours
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Villejuif, France, F-94805
- Institut Gustave Roussy
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Bologna, Italy, 40138
- University of Bologna Medical School
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Milan, Italy, 20141
- European Institute of Oncology
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Aarau, Switzerland, CH-5001
- Hirslanden Klinik Aarau
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Baden, Switzerland, CH-5404
- Kantonsspital Baden
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Basel, Switzerland, CH-4031
- Universitaetsspital-Basel
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Bellinzona, Switzerland, 6500
- Istituto Oncologico della Svizzera Italiana
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Bern, Switzerland, CH-3010
- Inselspital Bern
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Chur, Switzerland, CH-7000
- Kantonsspital Graubuenden
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Lausanne, Switzerland, CH-1011
- Centre hospitalier universitaire vaudois
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Olten, Switzerland, CH-4600
- Kantonsspital Olten
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St. Gallen, Switzerland, CH-9007
- Kantonsspital - St. Gallen
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Thonex-Geneve, Switzerland, CH-1226
- Hôpitaux Universitaires de Genève
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Winterthur, Switzerland, CH-8400
- Kantonsspital Winterthur
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Zurich, Switzerland, CH-8063
- City Hospital Triemli
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Zurich, Switzerland, CH-8091
- Universitaetsspital Zuerich
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Zurich, Switzerland, CH-8032
- Klinik Hirslanden
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Zurich, Switzerland, 8002
- Onkozentrum - Klinik im Park
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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.
|
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:
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
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Until treatment ends
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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.
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.
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
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Mantle-Cell
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Everolimus
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.