Lymphoma
Conditions
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
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.
Interventions
DRUGeverolimus
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.
GENETICmolecular 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
Sponsors
Swiss Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of the efficacy and tolerability of everolimus | Until treatment ends |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the efficacy of everolimus to induce molecular remission in patients treated with this regimen. | Until treament ends | — |
| Investigation of immunoglobulin heavy chain variable gene somatic hypermutations | 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. |
| Evaluation of a putative impact of Ig-V_H on clinical outcome. | Until treatment ends | — |
Countries
France, Italy, Switzerland
Outcome results
None listed