Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00516412
• Other study ID #: SAKK 36/06
• Secondary ID: EU-207492007-001
• Status: Completed
• Phase: Phase 2
• First received: August 14, 2007
• Last updated: September 28, 2015
• Start date: August 2007
• Est. completion date: August 2012

Study information

• Verified date: September 2015
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: August 2012
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

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

Locations

Country	Name	City	State
France	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
Italy	University of Bologna Medical School	Bologna
Italy	European Institute of Oncology	Milan
Switzerland	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	St. Gallen
Switzerland	Hopitaux Universitaires de Geneve	Thonex-Geneve
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	City Hospital Triemli	Zurich
Switzerland	Klinik Hirslanden	Zurich
Switzerland	Onkozentrum - Klinik im Park	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

France,  Italy,  Switzerland, 

References & Publications (1)

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 f — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the efficacy and tolerability of everolimus		Until treatment ends	No
Secondary	Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.		Until treament ends	No
Secondary	Investigation of immunoglobulin heavy chain variable gene somatic hypermutations	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	No
Secondary	Evaluation of a putative impact of Ig-V_H on clinical outcome.		Until treatment ends	No