Everolimus in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Genetic: molecular response by PCR; Drug: everolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT00516412

EU-20749

SAKK 36/06

2007-001108-19 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

35 participants in 1 patient group

Everolimus

Experimental group

Description:

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.

Treatment:

Drug: everolimus

Genetic: molecular response by PCR