-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 

-Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor, excluding small cell carcinoma
-Patients must have measurable disease
-Patients must have documented disease progression within 12 months of randomization
-Patients must not have clinically apparent CNA metastases or carcinomatous meningitis
-Patients must not have received prior temozolomide, DTIC, capecitabine, or 5 FU therapy.
-Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued greater than or equal to 4 weeks prior to randomization
-Concurrent somatostatin analogues are allowed provided that patients have been on stable doses for 8 weeks and have documented disease progression on that dose
-Chemoembolization is allowed if greater than or equal to 4 weeks from study entry.
-Patients may not be receiving Coumadin while on treatment. Other anticoagulants are allowed.
-Patients must have ECOG performance status 0-1

**Special Regulations**

Pharmacy License must be submitted to CTSU before patients may be enrolled.

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

Criteria
DISEASE CHARACTERISTICS:

Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology

Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., = 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology
Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy) required if the interval since tissue diagnosis of low-grade malignant lymphoma is > 24 months

Bone marrow biopsy alone not acceptable
Stage II, III, or IV AND grade 1, 2, or 3a disease
Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:

Patient must meet = 1 of the following GELF criteria:

Nodal or extranodal mass = 7 cm
At least 3 nodal masses > 3.0 cm in diameter
Systemic symptoms due to lymphoma or B symptoms
Splenomegaly with spleen > 16 cm by CT scan
Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
Leukemic presentation (= 5.0 x 10^9/L malignant circulating follicular cells)
Cytopenias (polymorphonuclear leukocytes < 1.0 X 10^9/L, hemoglobin < 10 g/dL, and/or platelets < 100 x 10^9/L)
Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):

Age = 60 years
Stage III-IV disease
Hemoglobin level < 12 g/dL
> 4 nodal areas
Serum LDH level above normal
At least 1 objective measurable disease parameter

Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization
Measurable disease in the liver is required if the liver is the only site of lymphoma
PATIENT CHARACTERISTICS:

See Disease Characteristics
ECOG performance status 0-2
ANC = 1,500/mm³ (includes neutrophils and bands)
Platelet count = 100,000/mm³
Creatinine = 2.0 mg/dL
AST and ALT = 5 x upper limit of normal (ULN)
Alkaline phosphatase = 5 x ULN
Total bilirubin = 1.5 x ULN (patients with known Gilbert disease should contact the study PI)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use 2 effective methods (1 highly effective and 1 additional effective method) of contraception = 28 days before, during, and for = 28 days after completing study treatment
HIV-positive patients must meet all of the following criteria:

HIV is sensitive to antiretroviral therapy
Must be willing to take effective antiretroviral therapy if indicated
No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis
No history of AIDS-defining conditions
If on antiretroviral therapy, must not be taking zidovudine or stavudine
Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and = 2 months following completion of study therapy or until the CD4 cells recover to over 250 cells/mm³
No recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for = 2 years
No active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
No = grade 2 neuropathy
No myocardial infarction within the past 6 months
No NYHA class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
No serious medical or psychiatric illness likely to interfere with participation in this clinical study
No known hypersensitivity to boron or mannitol
No chronic carriers of hepatitis B virus (HBV) with positive hepatitis surface antigen (HBsAg +)

Patients with a prior history of HBV infection, but immune, with only IgG hepatitis core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine 100 mg po daily) for = 1 week prior to course 1 and throughout induction and continuation therapy and for = 9 months after the last rituximab dose
Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® (for patients randomized to arm III)
PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma

Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy
A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed

Study Drugs: Provided: Sorafenib (pg 37), Sunitinib (pg 38)
** SURGEON MUST FILL OUT FORM PRIOR TO REGISTRATION ***

1) No prior anti-cancer therapy
2) No history of distant metastasis
3) No thyroid abnormalities
4) Must not have collecting duct carcinomas.
5) ECOG PS 0-1

**This study will be closed to accrual effective 09/20/13**

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

Criteria
DISEASE CHARACTERISTICS:

Histologically confirmed prostate cancer
Must have had definitive surgery, radiotherapy, or cryoablation
Must have hormone-sensitive prostate cancer by evidence of a serum total testosterone level > 150 ng/dL within the past 12 weeks
Biochemical failure after primary therapy and subsequent progression determined by 1 of the following:

PSA = 0.4 ng/mL for patients who had radical prostatectomy
PSA rise = 2 ng/mL above the nadir PSA for patients who had radiotherapy
Patients must have 2 subsequent PSA rises (PSA2 and PSA3) obtained = 2 weeks apart and each having a value higher than the previous one, with a PSA doubling time (PSADT) in 12 months

Baseline PSA = 2 ng/mL and = 50 ng/mL
No metastatic disease by physical exam, CT scan or MRI of the abdomen and/or pelvis, chest x-ray (or CT chest), and bone scan within the past 8 weeks
PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Granulocytes = 1,500/mm³
Platelet count = 100,000/mm³
Serum creatinine normal OR creatinine clearance = 60 mL/min
Total bilirubin = 1.5 times upper limit of normal (ULN)
Alkaline phosphatase = 2.5 times ULN
AST and ALT 2.5 times ULN
Fertile patients must use effective barrier method of contraception during and for 3 months after discontinuation of study treatment
Not HIV positive
No impaired cardiac function, including any of the following:

Baseline QTcF > 450 msec (male)
Congenital long QT syndrome
History of sustained ventricular tachycardia
Any history of ventricular fibrillation or torsades de pointes
Bradycardia defined as heart rate 50 beats per minute

Pacemaker and heart rate = 50 beats per minute allowed
Myocardial infarction or unstable angina within the past 6 months
NYHA class III or IV congestive heart failure
Right bundle branch block and left anterior hemi-block (bifascicular block)
No gastrointestinal (GI) disease resulting in inability to take oral medications, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn disease or ulcerative colitis)
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Akt inhibitor MK2206 or bicalutamide
No uncontrolled intercurrent illness including, but not limited to, any of the following:

Ongoing or active infection
Cardiac arrhythmia
Psychiatric illness and/or social situations that would limit compliance with study requirements
Patients with diabetes or at risk for hyperglycemia allowed provided it is controlled with oral agents
More than 2 years since another malignancy that has been adequately treated and the patient has been disease-free

No other currently active malignancy
PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Prior salvage therapy (surgery, radiotherapy, or other local ablative procedure) with curative intent within the past 4 weeks allowed
Prophylactic radiotherapy to prevent gynecomastia within the past 4 weeks allowed
Prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines, or experimental agents) within the past 4 weeks allowed provided PSA rise and PSADT were documented after the testosterone level > 150 ng/dL
At least 14 days since prior enzyme-inducing anti-epileptic drugs (EIAED)

Non-EIAED allowed
More than 2 weeks since prior and no concurrent cytochrome P450 EIAED (phenytoin, carbamazepine, or phenobarbital), St John wort, ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, or grapefruit juice
No prior therapy modulating testosterone levels (such as luteinizing hormone, releasing-hormone agonists/antagonists, or antiandrogens) within the past year

Prior therapy modulating testosterone levels in the neoadjuvant and/or adjuvant setting allowed
No concurrent 5-alpha-reductase inhibitors, ketoconazole, abiraterone, MDV31000, megestrol acetate, systemic steroids, or herbal supplements
No concurrent therapeutic administration of anticoagulant therapy

Low-dosage aspirin = 325 mg per day allowed
No other concurrent investigational agents or anticancer therapy (e.g., chemotherapy, immunotherapy, radiation therapy, surgery for cancer, or experimental medications)
No concurrent medications or substances that are inhibitors or inducers of CYP 450 3A4
No concurrent drugs with a risk of causing torsades de pointes