*Training required. Please check your site's credentialing status.*
SITES CURRENTLY CREDENTIALED:
Allegiance, Genesys Hurley, Livonia, Macomb, Oakland, Oakwood, Saginaw, St. Alphonsus, St. John, SJMH, Lehigh

Pre-Registration Eligibility:
-Histologically confirmed DLBCL expressing CD20 antigen. (Patients with transformed lymphoma, with known primary mediastinal large B-cell lymphoma, or  with composite lymphoma in the diagnostic tissue are excluded. Patients with DLBCL in primary diagnostic tissue but a bone marrow that shows low grade or indeterminate lymphoma are eligible.
-Patients must have stage II bulky disease, stage III, or stage IV.
-ECOG performance status must be 0-2
-Patients must be previously untreated and not receiving any other agent that would be considered as a treatment for the lymphoma. For patients with severe systemic symptoms, compressive disease, or rapidly progression symptomatic adenopathy, there is an allowance with up to 1mg/kg/day of prednisone, or equivalent, for a max of 7 days prior to beginning treatment.
-Patients must not have any known CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
-Must not have history of RT to greater than or equal to 25 % of the bone marror for other diseases or history of anthracycline therapy.
-Patients must not be receving erythroid stimulating agents.

Registration Eligibility:
-Must continue to meet pre-registration eligibility.
-Patients must have measurable disease.
-IPI must be 2 or greater.

1.0) Histologic or cytologic NSCL, pts must have recurrent dz after prior RT or surgery OR Stage IV dz OR Stage IIIB w/pleural or pericardial effusion seen on CXR or CT
2.0) Stage IV pt's with brain mets are eligible if brain mets are stable after txment with RT or surgery
3.0) Must have ECOG PS of ****2*****
4.0) Prior RT okay as long as it's not the only site of msble or evlble dz and the pt has recovered
5.0) No prior Chemo

ARM A  WILL BE CLOSED TO ACCRUAL EFFECTIVE APRIL 4, 2014 AS IT WILL HAVE MET ITS ACCRUAL GOAL

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
DISEASE CHARACTERISTICS:

?Diagnosis of melanoma of a cutaneous origin or unknown primary

?No ocular melanoma or melanoma of mucosal origin
?Stage IIIB, IIIC, or IV (M1a or M1b) disease

?Patients with stage IV melanoma must have normal LDH and distant skin, subcutaneous, lymph node, or lung metastases
?No other visceral metastases allowed
?Disease that has been completely resected with negative margins on resected specimens within the past 12 weeks

?Disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization

?Imaging studies must include a total body PET-CT scan (with or without brain) and brain MRI or CT (if MRI is contraindicated) (if PET-CT cannot be done, CT scan of neck, chest, abdomen, and pelvis should be done)
?Patients rendered free of disease by non-surgical means not allowed
?Disease recurrence after adequate surgical excision of original primary cutaneous melanoma allowed provided one of the following criteria are met:

?Recurrence in a regional lymph node basin after a prior complete lymph node dissection

?Relapsed disease must be completely surgically resected with free margins
?Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal, or lung metastases that are completely surgically resected with free margins
?Recurrence in a regional lymph node basin

?Relapsed disease must be completely surgically resected with free margins
PATIENT CHARACTERISTICS:

?ECOG performance status 0-1
?WBC ? 3,000/?L
?ANC ? 1,500/?L
?Platelet count ? 100,000/?L
?Hemoglobin ? 10 g/dL
?Serum creatinine ? 1.8 mg/dL
?AST and ALT ? 2.5 times upper limit of normal (ULN)
?Serum bilirubin < 2 times ULN (< 3 mg/dL in case of Gilbert syndrome)
?Not pregnant or nursing
?Negative pregnancy test
?Fertile patients must use adequate method of contraception throughout the study and for up to 26 weeks after the last dose of high-dose recombinant interferon alpha-2b (HDI)
?No active infection requiring concurrent treatment with parenteral antibiotics
?None of the following:

?Other significant medical, surgical, or psychiatric conditions
?Requirement for any medication or treatment that, in the opinion of the investigator, may interfere with compliance, make the administration of ipilimumab or HDI hazardous, or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
?No documented history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, or diverticulitis

?History of diverticulosis allowed
?No autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids or continuous use of topical steroid creams or ointments or ophthalmologic steroids

?History of occasional (but not continuous) use of steroid inhalers allowed
?None of the following:

?History of symptomatic autoimmune disease

?Rheumatoid arthritis
?Systemic progressive sclerosis (scleroderma)
?Systemic lupus erythematosus
?Sjögren syndrome
?Autoimmune vasculitis (e.g., Wegener granulomatosis)
?Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis)
?Other CNS autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
?Autoimmune hypothyroid disease or type 1 diabetes allowed provided replacement therapy is administered
?Not incarcerated or compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
?No other current malignancies except any prior in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, basal or squamous skin cancer, or other malignancies for which the patient has been disease free for > 5 years
?No active or chronic infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)

?Patients must have negative testing for HIV, HBV, and HCV within the past 4 weeks
PRIOR CONCURRENT THERAPY:

?See Disease Characteristics
?No prior adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after resection
?At least 30 days since prior radiotherapy, including after surgical resection
?No prior or concurrent anti-CTLA4 monoclonal antibodies, CTLA-4 inhibitor or agonist, CD137 agonist, or prior interferon-?
?At least 4 weeks since prior aldesleukin (IL-2), anti-tumor vaccine, or chemotherapy given before randomization
?No infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within the past 4 weeks
?No concurrent systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids

?Occasional but not continuous use of steroid inhalers allowed
?Systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids within the past 2 weeks allowed provided, in judgment of the treating physician investigator, that the patient is not likely to require resumption of treatment with these classes of drugs during the study
?Replacement doses of steroids for patients with adrenal insufficiency allowed
?No concurrent chemotherapy or radiotherapy
?No other concurrent anticancer or investigational agent

STUDY DRUG: Provided - Interferon alpha-2b (pg 16)
1) Melanoma of cutaneous origin (see pg 2 for elig criteria - staging)
2) Only initial presentation of primary melanoma eligible
3) Must complete all primary therapy & rando'ed within 84 days of wide excision
4) No prior RT or chemotx
5) ECOG PS: 0-1

-Diagnosis of CLL according to the NCI/IWCLL criteria or SLL according to the WHO criteria which includes previous:
--biopsy-proven small lymphocytic lymphoma OR
--diagnosis of CLL evidenced by the two following:
---peripheral blood lymphocyte count of greater than 5x10^9/L
---immunopheynotype consistent with CLL (the predominant population of lymphocytes share both B-cell antigens as well as CD5 in the absence of other pan-T-cell markers; clonality as evidenced by kappa or lambda light chain restriction)
OR
--negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy
-Patient must not have any prior chemotherapy or monoclonal anti-body therapy for treatment of CLL or SLL
-Patients must meet at least one of the following indications for treatment:
--evidence of progressive marrow failure as manifested by the development of worsening anemia and/or thrombocytopenia
--symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
--one or more of the following disease-related symptoms: weight loss greater than or equal to 10% within the previous 6mo; grade 2-3 fatigue attributed to CLL; fevers greater than 100.5 degF for 2 weeks without evidence of infection; clinically significant night sweats without evidence of infection)
--progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of greater than 50% over a two-month period or an anticipated doubling time of less than 6mo
-Patients must be 18-70 years old
-ECOG PS must be 0-2
-No deletion of 17p13 on cytogenetic analysis by FISH
-No radiation therapy within 4 weeks of registration. 

PLEASE NOTE: BONE MARROW BIOPSY MUST BE OBTAINED WITHIN 28 DAYS PRIOR TO REGISTRATION.  KIT must be used for BM for those who consented see section 10.1.1 for exclusions for those with BM collection prior to protocol screening/no kit was used.  

Step 0: Kit submission with blood and bone marrow for those that consented. 

Step 1 Eligibility:

-Patients must be diagnosed with symptomatic standard-risk multiple myeloma (SR-MM) as defined by all of the following:
--No evidence of t(4;14), t(14;16),t(14;20), or deletion 17p on FISH
--Standard risk gene expression profile (GEP)70 signature (only if GEP has been done and results are available)
--LDH less than or equal to 2 x ULN
--No more than 20% circulating plasma cells on WBC differential or 2,000 plasma cells/uL of peripheral blood
-Patients must have measurable or evaluable disease as defined by having one or more of the following:
--greater than or equal to 1g/dL M-protein on serum protein electrophoresis
--greater than or equal to 200 mg/24 hrs of monoclonal protein on a 24 hour urine protein electrophoresis
--involved free light chain greater than or equal to 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
--Monoclonal bone marrow plasmacytosis greater than or equal to 30% (evaluable disease)
-ECOG performance status 0-2 (PS 3 allowed if secondary to pain)
-Patients must have received no more than one cycle of prior chemotherapy and no more than 160mg of prior dexamethasone for treatment of symptomatic myeloma. They should not have been exposed to lenalidomide, bortezomib, or carfilzomib for treatment of symptomatic myeloma.
-Prior radiation therapy to symptomatic lesions is allowed provided 14d is between the end of RT and protocol treatment.

Step 2 Eligibility:

-Patients must not have experienced progression on induction therapy. and must not have received any non-protocol therapy outside of that assigned.
-Any adverse event related to step 1 therapy must have resolved to grade 2 or less

Lenalidomide Supply

Lenalidomide supply is not ordered via Biologics; use specialty pharmacy covered by the patient's insurance once registered to REMS. Participating pharmacy list in documents.

1.0) PS 0-2.
2.0) No concurrent or uncontrolled medical complications.
3.0) Must have received adequate prior chemo for myeloma including at least 4 cycles of combination chemo (i.e., VBMCP, VBAP, MP, etc....).


4.0) Must have measurable disease.

Drugs: Doxorubincin, Dexamethasone, Vincristine, PSC-833(provided).

*Open to the Asian and Native Hawaiian/ Pacific Islanders cohorts only at this time.** 

1.0) Must be receiving chemo for any malignancy, except leukemia.
2.0) Must have grade 2 or greater mucostitis.
3.0) PS 0-3.
4.0) Must not have infectious stomatitis or systemic infection.
5.0) No grade 3 or 4 vomiting.

Drug: Sucralfate (provided), Vitamin E (provided)

NOTE: this study is closed to accrual of  patients with non-measurable disease only.

*Credentials required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Allegiance, Genesys Hurley, Hurley, Livonia, Macomb, Oakwood, Oakland, Saginaw, St. Alphonsus, St. John, SJMH

-ER/PR positive histologically confirmed adenocarcinoma of the breast
-Patients whose tumors have HER2 IHC 3+, ISH greater than or equal to 2.0, or average HER2 copy number greater than or equal to 6.0 signals per cell are not eligible
-Patients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is not possible
-Must be postmenopausal or male 
-Patients must not have known central nervous system metastasis or CNS met history
-Patients must meet at least one of the following criteria:
--Disease progression after non-steroidal aromatase inhibitor (AI) use in the metastatic setting
--Relapse while on or within less than or equal to 12 mo of end of adjuvant non-steroidal AI therapy with no prior endocrine therapy for advanced disease. NOTE: Prior exemestane or fulvestrant is not allowed.
-Patients may have received one prior chemotherapy regimen for metastatic disease provided treatment was completed greater than or equal to 3 weeks prior to randomization.
-Patients may be treated with bone modifying agents such as bisphosphonates or receptor activator of nuclear factor kappa-B (RANK)-ligand agents (e.g. denosumab) per ASCO guidelines
-Prior radiotherapy must in general have been completed greater than or equal to 2 weeks prior to randomization and patients must have recovered from the toxicity of the radiation. NOTE: patients may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as sites of measurable or non-measurable disease outside the radiation therapy port are available to follow.
-Patients must not be receiving valproic acid, an HDAC inhibitor, and may not have previously received any HDAC inhibitor prior to enrollment
-Patients must have recovered from all clinically relevant AEs to grade 1 or baseline due to previous agents administered (except alopecia)
-Patients must have ECOG performance status 0-1