Everolimus in Treating Patients With Lymphoma That Has Relapsed or Not Responded to Previous Treatment
Condition: Leukemia; Lymphoma; Lymphoproliferative Disorder
MeSH terms: Lymphoma; Leukemia; Lymphoproliferative Disorders
Intervention: Everolimus
Intervention description: Everolimus 10 mg orally daily for 4 week cycle. Repeat until progression, unacceptable toxicity, refusal, or alternative therapy at any time.
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 277.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; small intestine lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult T-cell leukemia/lymphoma; recurrent grade 3 follicular lymphoma; recurrent marginal zone lymphoma; refractory chronic lymphocytic leukemia; recurrent small lymphocytic lymphoma; recurrent mycosis fungoides/Sezary syndrome; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; recurrent adult diffuse large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent mantle cell lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; post-transplant lymphoproliferative disorder; recurrent adult diffuse small cleaved cell lymphoma

Summary:

      RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the cancer.

      PURPOSE: This phase II trial is studying the side effects and how well everolimus works in
      treating patients with lymphoma that has relapsed or not responded to previous treatment.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Biopsy-proven* relapsed or refractory lymphoma, including the following:

               -  Aggressive lymphoma (closed to accrual as of 2/7/08 except for diffuse large B
                  cell lymphoma, grade III follicular lymphoma, or transformed lymphoma)

                    -  Transformed lymphoma

                    -  Diffuse large B-cell lymphoma

                    -  Mantle cell lymphoma

                    -  Grade 3 follicular lymphoma

                    -  Precursor B-cell lymphoblastic leukemia/lymphoma

                    -  Mediastinal (thymic) large B-cell lymphoma

                    -  Burkitt's lymphoma/leukemia

                    -  Precursor T-cell lymphoblastic leukemia/lymphoma

                    -  Primary cutaneous anaplastic large cell lymphoma

                    -  Primary systemic type anaplastic large cell lymphoma

               -  Indolent lymphoma (closed to accrual as of 8/18/08)

                    -  Small lymphocytic lymphoma/chronic lymphocytic leukemia

                    -  Grade 1 or 2 follicular lymphoma

                    -  Extranodal marginal zone B-cell lymphoma of MALT type

                    -  Nodal marginal zone B-cell lymphoma

                    -  Splenic marginal zone B-cell lymphoma

               -  Uncommon lymphoma (closed to accrual as of 9/2/08)

                    -  Unspecified peripheral T-cell lymphoma

                    -  Anaplastic large cell lymphoma (T and null cell type)

                    -  Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)

                    -  Central Nervous System (CNS) lymphoma

                    -  Post-transplant lymphoproliferative disorder

                    -  Mycosis fungoides/Sezary syndrome

                    -  Hodgkin's lymphoma

                    -  Primary effusion lymphoma

                    -  Blastic Natural Killer(NK)-cell lymphoma

                    -  Adult T-cell leukemia/lymphoma

                    -  Nasal type extranodal NK/T-cell lymphoma

                    -  Enteropathy type T-cell lymphoma

                    -  Hepatosplenic T-cell lymphoma

                    -  Subcutaneous panniculitis-like T-cell lymphoma

                    -  Angioimmunoblastic T-cell lymphoma

        NOTE: *Biopsies performed < 6 months prior to study entry are allowed; biopsy-proven CNS
        lymphoma (at any time) does not require a re-biopsy in order to be eligible for this study

          -  Previously treated disease

               -  Patients with aggressive lymphoma (closed to accrual as of 8/24/07) OR Hodgkin's
                  lymphoma must have received or be ineligible for potentially curative therapy,
                  including stem cell transplantation

          -  Measurable disease** by CT scan or MRI, defined by 1 of the following:

               -  At least 1 unidimensionally measurable lesion > 2 cm in diameter

                    -  Skin lesions may be used if they meet this criterion and are photographed
                       with a ruler

               -  More than 5,000/mm³ tumor cells in the blood

        NOTE: **For patients with lymphoplasmacytic lymphoma without measurable lymphadenopathy,
        measurable disease may be defined by bone marrow lymphoplasmacytosis with > 10%
        lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or
        lymphoplasmacytic cells on bone marrow biopsy AND quantitative Immunoglobulin M(IgM)
        monoclonal protein > 1,000 mg/dL

        PATIENT CHARACTERISTICS:

          -  Eastern Cooperative Oncology Group(ECOG) performance status 0-2

          -  Life expectancy > 3 months

          -  Absolute neutrophil count ≥ 1,000/mm³

          -  Platelet count ≥ 75,000/mm³

          -  Hemoglobin ≥ 8 g/dL

          -  Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times
             ULN

          -  aspartate aminotransferase(AST) ≤ 3 times ULN (5 times ULN if liver involvement is
             present)

          -  Creatinine ≤ 2 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Willing to provide blood samples and portion of bone marrow aspirate and biopsy during
             study participation

          -  Able to swallow intact study medication tablets

          -  No other life-threatening illness (unrelated to tumor)

          -  No serious non-malignant disease (e.g., active infection or other condition) that, in
             the opinion of the investigator, would preclude study participation

          -  No other active malignancy requiring treatment or that would preclude study
             participation

          -  No known HIV positivity

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 3 weeks since prior myelosuppressive chemotherapy or biologic therapy (unless
             the patient has recovered from the nadir of the previous treatment)

          -  More than 3 weeks since prior radiotherapy (unless the acute side effects associated
             with therapy are resolved)

          -  Concurrent stable (i.e., not increased within the past month) chronic doses of
             corticosteroids, with a maximum dose of 20 mg of prednisone per day, is allowed if
             prescribed for disorders other than lymphoma (e.g., rheumatoid arthritis, polymyalgia
             rheumatica, adrenal insufficiency, or asthma)

               -  Non-escalating doses of steroids at the lowest possible dosing level are allowed
                  for CNS lymphoma

          -  No other concurrent investigational ancillary therapy

          -  No other concurrent chemotherapy, immunotherapy, or radiotherapy

          -  No concurrent participation in any other clinical trial involving a pharmacologic
             agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or
             therapeutic intent