-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 biopsywithin 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

STEP 1: Registration to Arm A, B, C

1. Patients must have histologically confirmed adenocarcinoma of the breast at

significant risk of distant recurrence based on at least one of the following criteria: Involvement of at least one axillary lymph node on routine histologic

examination. Patients with axillary node involvement only demonstrated

by immunohistochemistry are not eligible unless they meet one of the

other eligibility criteria below. ER negative tumor >1 cm, ER+ tumor > 5 cm regardless of recurrence score, ER+ tumor >1 cm but < 5 cm with a recurrence score > 11. (Patients enrolled in the TAILORx trial are eligible.)

NOTE: Premenopausal patients with ER+ tumor may participate in the

IBCSG SOFT trial. NOTE: Premenopausal patients with ER- tumor may participate in S0230.

2. Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, breast conservation surgery and axillary dissection or breast conservation surgery and sentinel node biopsy.

NOTE: Axillary dissection is strongly encouraged in patients with lymph node

involvement identified on sentinel node biopsy. NOTE: Breast conservation surgery includes lumpectomy, partial mastectomy, and excisional biopsy.

3. Margins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS). Patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible.

4. Interval between last surgery for breast cancer (breast conservation surgery, mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast conservation surgery margins) and Day 1 of treatment must be > 28 days and < 84 days.

5. ECOG performance status of 0-1

6. Patients must have adequate organ function within < 8 weeks prior to randomization, as measured by:

Absolute neutrophil count > 1000/mm3

Platelet count > 100,000/mm3

Total bilirubin < 1.5 mg/dL

AST < 2 upper limit of normal

Serum creatinine < 1.5 mg/dL

Urine protein: creatinine (UPC) ratio <1.0*

PTT < 1.5 x normal X ULN

LVEF > institutional limits of normal by MUGA or ECHO

* Please see Appendix V for instructions on how to obtain the urine

protein:creatinine ratio

7. Patients who have undergone breast conservation surgery must receive radiation. Prior to randomization, the investigator must specify the planned radiation technique. NOTE: If APBI was completed prior to study entry, day 1 of protocol therapy must be at least 4 weeks after the completion of APBI.

8. Post-mastectomy RT is required for all patients with a primary tumor of > 5 cm or involvement of 4 or more lymph nodes. Post-mastectomy RT may be administered at the investigator?s discretion for all other mastectomy patients.

9. Patients with HER2 + (3+ by IHC or FISH+) breast cancer are not eligible.

10. Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher TNM stage tumor meets the eligibility criteria for this trial.

11. Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes at diagnosis.

12. Patients must not have received prior cytotoxic chemotherapy or hormonal therapy for this breast cancer. Prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed. NOTE: Prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry. Similarly, prior raloxifene use is allowed but must be discontinued at study entry.

13. Patients must not have had any major surgical procedure within 28 days of day 1 treatment. NOTE: Non-operative biopsy or placement of a vascular access device is not considered a major surgery.

14. Patients may not have had placement of a vascular access device within 24 hours of planned Day 1 of treatment.

15. Patients must not have clinically significant cardiovascular or cerebrovascular disease, including:

Any history of

? Cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage

? Ischemic bowel

Within the last 12 months

? Myocardial infarction

? Unstable angina

? New York Heart Association (NYHA) grade II or greater congestive heart

failure

? Grade II or greater peripheral vascular disease

NOTE: See Appendix X for NYHA classification and peripheral vascular disease

grading criteria

Active at study entry

? Uncontrolled hypertension defined as SBP > 160 or DBP > 90

? Uncontrolled or clinically significant arrhythmia.

NOTE: Patients with controlled atrial fibrillation are eligible.

16. Patients who require full dose anticoagulation may enroll provided they meet the following criteria:

? the patient must have an in-range INR (usually between 2 and 3) on a stable

dose of warfarin or be on stable dose of LMW heparin.

? the patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. varices)

NOTE: Prophylactic use of anticoagulants to maintain patency of a vascular access device is permitted.

17. Patients must not have a bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathy.

18. Patients must not have a non-healing wound or fracture. Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization are not eligible.

19. Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies.

20. Male or female patients age > 18 years of age are eligible.

21. Women must not be pregnant or breast-feeding due to the potential harmful effects of bevacizumab on the developing fetus. All females of childbearing potential must have a blood or urine test within 7 days prior to randomization to rule out pregnancy.

22. Women of childbearing potential and sexually active males must use an accepted and effective method of contraception.



STEP 2: Unblinding and Re-registration to Arm D

1. Only Step I patients treated on Arm C who have not ended treatement per section 5.7 are eligible to register to Step 2, Arm D.