Clinical trial NCT00516412: Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2007-08-15
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Evaluation of the efficacy and tolerability of everolimus
timeFrame: Until treatment ends
Secondary outcomes:
measure: Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen.
timeFrame: Until treament ends
measure: Investigation of immunoglobulin heavy chain variable gene somatic hypermutations
timeFrame: Until treatment ends
measure: Evaluation of a putative impact of Ig-V_H on clinical outcome.
timeFrame: Until treatment ends
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bologna
country: Italy
facility: University of Bologna Medical School
city: Milan
country: Italy
facility: European Institute of Oncology
city: Aarau
country: Switzerland
facility: Hirslanden Klinik Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thonex-Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Onkozentrum - Klinik im Park
city: Zurich
country: Switzerland
facility: Klinik Hirslanden
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: UniversitaetsSpital Zuerich
name: Christoph Renner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.