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Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00516412
First received: August 14, 2007
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: everolimus
Genetic: molecular response by PCR
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Evaluation of the efficacy and tolerability of everolimus [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen. [ Time Frame: Until treament ends ] [ Designated as safety issue: No ]
  • Investigation of immunoglobulin heavy chain variable gene somatic hypermutations [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]
    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. [ Time Frame: Until treatment ends ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: August 2007
Study Completion Date: August 2012
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516412

Locations
France
CHU de Grenoble - Hopital de la Tronche
Grenoble, France, 38043
Hopital Haut Leveque
Pessac, France, 33604
Centre Hospitalier Universitaire Bretonneau de Tours
Tours, France, 37044
Institut Gustave Roussy
Villejuif, France, F-94805
Italy
University of Bologna Medical School
Bologna, Italy, 40138
European Institute of Oncology
Milan, Italy, 20141
Switzerland
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Olten
Olten, Switzerland, CH-4600
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Hopitaux Universitaires de Geneve
Thonex-Geneve, Switzerland, CH-1226
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
City Hospital Triemli
Zurich, Switzerland, CH-8063
Klinik Hirslanden
Zurich, Switzerland, CH-8032
Onkozentrum - Klinik im Park
Zurich, Switzerland, 8002
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Principal Investigator: Christoph Renner, MD UniversitaetsSpital Zuerich
  More Information

Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00516412     History of Changes
Other Study ID Numbers: SAKK 36/06, EU-20749, EUDRACT-2007-001108-19
Study First Received: August 14, 2007
Last Updated: August 7, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
recurrent mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014