**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

 

1.0) =18 and = 56yrs
2.0) No previous Chemo for AML (hydroxyurea OK)
3.0) PS 0-1

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

-Diagnosis of asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 60 mo meeting both of the following criteria:
--Bone marrow plasmacytosis with greater than or equal to 10% plasma cells or sheet of plasma cells by bone marrow aspiration and/or biopsy within 4 weeks of randomization
--Abnormal serum free-light chain ratio (< 0.26 or > 1.65) by serum FLC assay
-Patients must have measurable monoclonal protein (M-protein): greater than or equal to 1g/dL on serurm protein electrophoresis or greater than or equal to 200 mg/24 hrs urine protein electrophoresis
-Patients must have no lytic lesions or hypercalcemia
-No prior or concurrent systemic or radiation therapy for the treatment of myeloma
-Concurrent use of bisphosphonates is not permitted; however, once-a-year IV bisphosphonate for osteoporosis is permitted
-Prior or concurrent use of erythropoietin is not allowed
-Prior glucocorticosteroid therapy for MM is not allowedNo monoclonal gammopathy of undetermined significance
-Patients must not have baseline bone lesions or plasmacytomas
-Patients with monoclonal gammopathy of undetermined significance are not eligible
-ECOG performance status must be 0-2
-Patients must be felt to not have an immediate need for chemotherapy

 *Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Genesys Hurley, Hurley

DISEASE CHARACTERISTICS:

Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:

Grade 2 astrocytoma
Grade 2 oligodendroglioma
Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)
NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time
Paraffin-embedded tumor specimen available for submission for confirmation of pathological diagnosis and determination of 1p and 19q deletion status
Patients must currently meet = 1 of the following criteria*:

Uncontrolled symptoms, defined as any of the following:

Headaches associated with mass effect
Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)
Focal neurological symptoms
Cognitive symptoms or deficits
Tumor progression by serial MRIs, defined as any of the following:

New or progressive enhancement
New or progressive T2 or FLAIR signal abnormality
Age = 40 years
NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs AND who have no evidence of radiographic progression are not eligible.
Patients who have undergone gross total resection and have no detectable residual disease are eligible
No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors
PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
WBC = 3,000/mm^3
ANC = 1,500/mm^3
Platelet count = 100,000/mm^3
Hematocrit = 30%
Bilirubin = 2 times upper limit of normal (ULN)
AST and ALT = 3 times ULN
Creatinine = 2.0 times ULN
Not pregnant or nursing
Negative pregnancy test
Able to undergo MRI with and without contrast
No other malignancy within the past 5 years, except for nonmelanoma skin cancer or cervical carcinoma in situ
No uncontrolled infection
No known HIV positivity
No medical disorder that would increase risks associated with radiotherapy and temozolomide
No other disorder that would limit life expectancy to < 5 years
PRIOR CONCURRENT THERAPY:

No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational therapy directed at the brain tumor

Any number of prior surgical procedures for the brain tumor allowed
No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the brain
At least 2 weeks since prior brain surgery