This randomized phase I/II trial studies the side effects and the best dose of temsirolimus when given together with bortezomib, rituximab, and dexamethasone and to see how well they work compared to bortezomib, rituximab, and dexamethasone alone in treating patients with untreated or relapsed Waldenstrom macroglobulinemia or relapsed or refractory mantle cell or follicular lymphoma. Bortezomib and temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. Monoclonal antibodies, such as rituximab, can block cancer growth in difference ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bortezomib, rituximab, and dexamethasone are more effective with temsirolimus in treating non-Hodgkin lymphoma.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of temsirolimus in combination with bortezomib, rituximab, dexamethasone in patients with relapsed Waldenstrom's macroglobulinemia and relapsed/refractory mantle cell, follicular, marginal zone or small lymphocytic lymphoma. (Phase I) II. To evaluate whether the addition of temsirolimus to the regimen of bortezomib, rituximab, dexamethasone improves progression-free survival in patients with previously untreated or relapsed Waldenstrom's macroglobulinemia. (Phase II)

SECONDARY OBJECTIVES:

I. To define and describe the toxicities of temsirolimus in combination with bortezomib, rituximab, and dexamethasone. (Phase I) II. To evaluate time to progression of bortezomib, rituximab, dexamethasone +/- temsirolimus in patients. (Phase II) III. To evaluate major and minor response by 6 cycles of therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) IV. To evaluate time to response and duration of response of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) V. To evaluate toxicity of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VI. To evaluate time to next therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VII. To evaluate overall survival of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VIII. To describe treatment-related fatigue, physical and functional well-being during and after treatment. (Phase II) IX. To compare the change in treatment related fatigue, physical and functional well-being over 6 cycles of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Quality of Life) X. To prospectively assess health-related quality of life longitudinally (pre-treatment to 3 year follow-up assessment) among trial participants. (Quality of Life) XI. To describe treatment-related peripheral neuropathy associated with bortezomib neurotoxicity. (Quality of Life)

OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a randomized phase II study.

PHASE I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only); and bortezomib IV or subcutaneously (SC) and dexamethasone orally (PO) on days 1, 8, and 15. Courses repeat every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only) and bortezomib IV or SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and rituximab, bortezomib, and dexamethasone as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

Inclusion Criteria:

• Histologically proven diagnosis

• For phase I portion (Arm A, B, C and D), patients must have of one of the following:

  • Relapsed Waldenstrom's macroglobulinemia
  • Relapsed/refractory mantle cell lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
  • Relapsed/refractory follicular lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
  • Relapsed/refractory marginal zone lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
  • Relapsed/refractory small lymphocytic lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen

• For phase II portion (Arm E and F), patients must have a diagnosis of symptomatic Waldenstrom's macroglobulinemia, either untreated or relapsed, confirmed by the presence of all of the following:

  • Bone marrow lymphoplasmacytosis with

    • >= 10% lymphoplasmatic cells (measured within 28 days prior to registration) OR
    • Aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 28 days prior to registration)

  • Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal protein of >= 1000 mg/dL obtained within 28 days prior to registration

  • Cluster of differentiation 20 (CD20) positive bone marrow or lymph node by immunohistochemistry or flow cytometry obtained within 28 days prior to registration

  • Lymph node biopsy must be done =< 28 days prior to registration if used as an eligibility criterion for study entry

  • Serum protein electrophoresis (SPEP) is required to be performed within 28 days prior to registration

• Additional requirements for Waldenstrom's macroglobulinemia (WM) patients (phase I and II):

• In addition to measurable disease, patients must have symptomatic disease defined by one or more of the following:

  • Laboratory studies defining eligibility (hemoglobin [Hgb], platelet count, viscosity) must have been obtained within 28 days prior to registration; if more than one test was obtained, the most recent one will be utilized

  • Hemoglobin =< 11 g/dL

  • Hyperviscosity syndrome or measured viscosity level of >= 4 centipoise

    • NOTE: for these patients it is strongly recommended that they undergo therapeutic plasmapheresis prior to initiation of therapy

  • Platelet count < 100,000/mm^3

  • Symptomatic lymphadenopathy, splenomegaly, or hepatomegaly

  • Constitutional symptoms including fever, night sweats, or unexplained weight loss (at least 10% of body weight in < 6 months)

  • Symptomatic cryoglobulinemia

• Additional requirements for WM patients (phase I):

  • Patients must have received previous treatment with at least one standard regimen and are no longer responsive to that regimen
  • There must have been at least 21 days since the last regimen and patient must have recovered from any previous treatment-related toxicity to =< grade 1

• Additional requirements for WM patients (phase II):

  • For previously treated patients, no more than 4 prior regimens are allowed
  • If last regimen is with rituximab there must have been at least 6 months since last rituximab dose, and if without rituximab there must have been at least 3 months since last regimen

• For all phase I patients, there must have been at least 21 days since last regimen and any previous non-hematologic treatment related toxicity must have resolved to =< grade 1

• Patients must not be receiving concurrent steroids > 10 mg prednisone (or equivalent) per day

• Prior irradiation is allowed if >= 28 days prior to registration have elapsed since the date of last treatment

• Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x institutional upper limit of normal (ULN), within 28 days prior to registration

  • NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication; patients cannot be enrolled if they do not meet these criteria on or off lipid lowering medication; patients must start lipid lowering medication and cholesterol and triglycerides must be below said levels before study entry

• Patients must not have had prior exposure to mammalian target of rapamycin (m-TOR) inhibitors (sirolimus, temsirolimus, everolimus)

• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception throughout the study and for 8 weeks following discontinuation of everolimus

• Patients must have no history of prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in-situ cervical cancer; the patient may also have had other cancer for which the patient was curatively treated with surgery alone and from which the patient has been disease free for >= 5 years

• Platelets >= 75,000 mm^3

• Neutrophils >= 1,000 mm^3

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN

• Direct bilirubin =< 1.5 mg/dL

• Serum creatinine =< 2.5 mg/dL

• Patients must be tested for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) within 28 days of registration and will not be eligible if found to be positive

• Patients must not have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study, including, but not restricted to:

  • Symptomatic congestive heart failure of New York Heart Association class III or IV
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 3 months of start of study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease
  • Severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for Hgb) that is < 50% of the normal predicted value and/or oxygen (O2) saturation < 88% at rest on room air
  • Active (acute or chronic) or uncontrolled severe infections

• Patients must have Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status of =< 2

• Patients must not have grade 2 or higher neuropathy

• Patients must not have concurrent use of angiotensin-converting enzyme (ACE) inhibitors (angioedema), and no concurrent use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and inhibitors