Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT ID: NCT00516412

Last Updated: 2015-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2012-08-31

Brief Summary

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.

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

everolimus

Intervention Type: DRUG

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.

molecular response by PCR

Intervention Type: GENETIC

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

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: GENETIC

Other Intervention Names

RAD001

Eligibility Criteria

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

• 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

• 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:

• 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:

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Renner, MD

Role: PRINCIPAL_INVESTIGATOR

UniversitaetsSpital Zuerich

Locations

CHU de Grenoble - Hopital de la Tronche

Grenoble, , France

Hopital Haut Leveque

Pessac, , France

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

Institut Gustave Roussy

Villejuif, , France

University of Bologna Medical School

Bologna, , Italy

European Institute of Oncology

Milan, , Italy

Hirslanden Klinik Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopitaux Universitaires de Geneve

Thonex-Geneve, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Onkozentrum - Klinik im Park

Zurich, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

France; Italy; Switzerland

References

Renner C, Zinzani PL, Gressin R, Klingbiel D, Dietrich PY, Hitz F, Bargetzi M, Mingrone W, Martinelli G, Trojan A, Bouabdallah K, Lohri A, Gyan E, Biaggi C, Cogliatti S, Bertoni F, Ghielmini M, Brauchli P, Ketterer N; Swiss SAKK and French GOELAMS group from European Mantle Cell Lymphoma Network. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Haematologica. 2012 Jul;97(7):1085-91. doi: 10.3324/haematol.2011.053173. Epub 2012 Feb 7.

Reference Type: RESULT

PMID: 22315486 (View on PubMed)

Other Identifiers

EU-20749

Identifier Type: -

Identifier Source: secondary_id

2007-001108-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAKK 36/06

Identifier Type: -

Identifier Source: org_study_id