Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Inclusion Criteria:

• Histologically confirmed mantle cell lymphoma meeting the following criteria:

  • Diagnosis confirmed by initial biopsy or at time of relapse

    • No bone marrow biopsy as sole means of diagnosis

      • May be used in conjunction with nodal biopsies
    • No fine needle aspirates
  • CD5-positive, CD23-negative, and cyclin D1-positive by flow cytometry or immunohistochemistry

• Measurable disease, defined as any tumor mass > 1cm by physical examination, CT scan, MRI, or conventional radiograph

  • No nonmeasurable disease only, including any of the following:

    • Bone lesions (should be noted, if present)
    • Ascites
    • Pleural or pericardial effusion
    • Lymphangitis cutis or pulmonis
    • Bone marrow (involvement by non-Hodgkin lymphoma should be noted)

• Received prior therapy with at least 1 regimen, which may have been single- or multi-agent, and consisted of traditional cytotoxic and/or biologic agents

  • Must have progressive or refractory disease following initial regimen

    • Refractory disease defined as stable or progressive disease as best response to prior therapy, or complete or partial response as initial response followed by disease progression within 6 months
• No known CNS involvement by lymphoma
• ECOG performance status 0-2
• ANC ≥ 1,000/μL (≥ 500/μL if marrow involvement)
• Platelet count ≥ 75,000/μL
• Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless attributable to Gilbert disease)
• Creatinine ≤ 1.5 times ULN (unless attributable to non-Hodgkin lymphoma) AND estimated creatinine clearance ≥ 30 mL/min (patients on dialysis are not eligible)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile women must use effective double-barrier contraception during and for at least 28 days after completion of lenalidomide therapy
• Men must use effective contraception during and for 28 days after completion of lenalidomide therapy, even if they have undergone a successful vasectomy
• No peripheral neuropathy ≥ grade 3 within the past month

• Patients with HIV infection are eligible, provided they meet the following criteria:

  • CD4-positive cell count > 350/mm^3
  • Must have treatment-sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3
  • No history of AIDS-defining conditions or other HIV-related illnesses
  • No concurrent zidovudine or stavudine because of overlapping toxicities with protocol therapy
• No deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within the past 3 months * Patients with a distant history (> 3 months prior to study entry) of DVT/PE are eligible, provided they receive concurrent prophylactic aspirin or low molecular weight heparin, unless contraindicated
• LVEF ≥ 45% by MUGA scan or ECHO
• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past 6 months
• No known positivity for hepatitis A, B, or C
• No concurrent dexamethasone or other steroidal antiemetics
• No concurrent hormones used as chemotherapy or other chemotherapeutic agents except for steroids given for adrenal failure (hormones administered for non-disease related conditions [e.g., insulin for diabetes or birth control pills])
• No prior bortezomib or lenalidomide

• Prior autologous stem cell transplantation (SCT) allowed

  • No prior allogeneic SCT allowed
• No prior radioimmunotherapy within the past 12 months

• More than 2 weeks since prior corticosteroids, except maintenance therapy for a non-malignant disease

  • Maintenance therapy dose may not exceed20 mg/day prednisone or equivalent
• No other concurrent investigational or commercial agents or therapies for lymphoma