Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: everolimus
* Genetic: molecular response by PCR


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus<br>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<br>* 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.<br>* Other names: RAD001;Genetic: molecular response by PCR<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy and tolerability of everolimus |  | Until treatment ends | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 
| Evaluation of a putative impact of Ig-V_H on clinical outcome. |  | Until treatment ends | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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