-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

-Pathologically confirmed renal cell with a clear cell component. Pure papillary and chromophobe histologies are excluded. There must be pathologic confirmation of metastic disease in the metastatectomy specimen.
-Undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past).
-Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization.
-Patients with synchronous disease at initial diagnosis must have metastatic disease.
-Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease.
-Patients presenting with tumors within the kidneys are not eligibile if there are no extrarenal sites of disease
-Patients must have no evidence of disease on post-operative imaging
-Patients must not have received any prior or concurrent systemic therapy for RCC.
-Must have no prior history or current clnically apparent central nervous system metastasis.
-ECOG PS must be 0-1
-Patient must not be taking drugs known to prolong the QTc interval.

 *Training required. Please check your site's credentialing status.* 

Step 1 Eligibility:
-Patient must have documented diagnosis of MDS lasting at least three months according to WHO criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (WBC < 12,000/mcL)
-Patient must have International Prognostic Scoring System (IPSS) categories of Low- or Intermediate-1-risk disease. Patients with cytogenetic failure and < 10% marrow blasts will be eligible.
-Patients must have symptomatic anemia untransfused with hemoglobin less than 9.5 g/dL less than or equal to 8 weeks prior to randomization or with RBC transfusion-dependence confirmed for less than or equal to 8 weeks before randomization.
-For patients without the deletion 5q31.1: Patients must have failed treatment with an erythropoietic growth factor or have a low probability of response to rhu-erythropoietin.
-Patients must be off all non-transfusion therapy for MDS for 28 days prior to initiation of study treatment. Patients may receive hydrocortisone prophylactically to prevent transfusion reactions.
-Patients must not have documented iron deficiency.
-Patients must not have prior therapy with lenalidomide.
-Patients must not have proliferative chronic myelomonocytic leukemia
-Patients must not have MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases
-Patients must not have used cytotoxic chemotherapeutic agents or experimental agents for the treatment of MDS within 8 weeks of randomization

Crossover Registration Eligibility:
-Patients must have completed 16 weeks of monotherapy with lenalidomide
-Patients must show failure to achieve Major Erythroid Response or have achieved MER but relapsed
-Patients must not have a limiting unresolved grade 3 or greater toxicity from lenalidomide monotherapy or drug intolerance

1.0) Histologic proof of AML.
2.0) Bone marrow Asp & Bx prior to study entry is sent to ECOG(see Appendix IV)
3.0) Must have 1 of the following: 1) relapse =6mo's after 1st CR, OR 2)refractory to initial TX, OR 3)relapsed after BMT, OR 4)2nd or greater relapse, OR 5) 2ndary AML and AML evolving from MDS or MPD, OR 6) High risk MDS-see protocol definition

4.0) Age = 70.
5.0) Prior tx with >550 mg/m2 doxorubicin or >800 mg/m2 daunorubicin is allowed.
6.0) MUGA >50%

Drug: Cytarabine, Mitoxantrone, VP-16, PSC 833 (provided)

1.0) Pt. must be ineligible for or refuse E1A95
2.0) Pt. must have a diagnosis of multiple myeloma confirmed by the presence of bone marrow plasmacytosis with > 10% plasma cells, sheets of plasma cells, or biopsy proven plasmacytoma.
3.0) Pt. must ahve documentation of at least ONE of the criteria listd below: 1. Myeloma (M) protein in the serum, or 2. M-protein in the urine.
4.0) Pt. must have measurable disease. (lytic bone lesions, anemia, BM plasmocytosis and beta-2 microglobulin in the serum do not qualify for measurable disease).
5.0) Pt. must have received prior chemo including at least 4 cycles of combination chemo (i.e. VBMCP, VBAP, MP, etc).
6.0) Pt. who have received >2 prior combination chemo regimens are ineligible.
Drug: Taxotere (provided)

 *Training required. Please check your site's credentialing status.*

-Unresectable stage lll or stage lV melanoma, either initial presentation or recurrent, that is of cutaneous origin or unknown primary origin and that is histologically diagnosed.
-No more than one prior systemic therapeutic regimen for unresectable stage lll or stage lV melanoma.
-ECOG performance status of 0-
-No history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed).
-Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids including oral steroids or continuous use of topical steroid creams or ointments or ophthalmologic steroids.
-Exclusion from this study also includes patients with a history of symptomatic autoimmune disease.
-Patients must be free of brain metastasis

Participation in E3903 is mandatory for all ECOG-coordinated and designated intergroupcoordinated

Leukemia treatment trials which require pre-treatment central assessments for

patient eligibility determination or treatment assignment. This requirement for E3903

participation will be stated in the treatment trial.

For all other leukemia treatment trials, participation in E3903 is not mandatory but may

facilitate the submission of baseline specimen requirements for evaluability assessments,

correlative components, or verification of diagnosis for participation in the considered

treatment trials.

**Data done in RAVE**

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No