*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health SJMH IHA (Brighton, Ann Arbor, Chelsea, Canton), Livonia, Genesys, Sparrow, Lehigh

Eligibility Criteria:

3.2.1 Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features following complete resection of the primary tumor (radical or partial nephrectomy). Note: Patients with microscopically positive soft tissue or vascular margins without gross residual disease are permitted.

*Intermediate-high risk RCC:

• pT2 Grade 4 or sarcomatoid features, N0M0

• pT3 any grade N0, M0 

OR  

*High-risk RCC

• pT4, any grade, N0, M0

• pT, any stage., any grade, N+, M0

OR 

*cM1 NED RCC

• Participants who have had resection of primary tumor (radical or partical nephrectomy) and resection or definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) at the time of primary tumor removal (synchronous) or ≤1 year from primary tumor removal (metachronous).  

3.2.2 Surgery (radical or partial nephrectomy or metastasectomy or ablation) >4 weeks but ≤ 16 weeks prior to study registration with no ongoing complications from surgery

3.2.3 No evidence of disease at time of randomization as assessed by investigator by either CT or MRI scan of the brain and chest, abdomen and pelvis

3.2.4 No prior systemic treatment for RCC 

3.2.5 Age ≥ 18 years

3.2.6 ECOG performance status ≤ 2 (or Karnofsky ≥ 60%). 

3.2.7 Required Initial Laboratory Values:

Absolute Neutrophil Count (ANC) ≥ 1,000/mm3

Platelet Count ≥ 100,000/mm3a

Hemoglobin ≥ 8 g/dL

Total Bilirubin ≤ 1.5 x upper limit of normal (ULN)

AST (SGOT)/ALT (SGT) ≤ 3 x upper limit of normal (ULN)

Calc. Creatinine Clearance ≥ 30 mL/min (using Cockcroft Gault equation or the estimated glomerular filtration rate from the modification of diet in renal disease trial)

Urine Protein ≤ 1+ on UA or UPCR < 2mg/mg 

**PLEASE SEE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: SJMH (Ann Arbor, Brighton, Chelsea, Canton, St. Mary's Livonia, Genesys, LVHN

Eligibility Criteria:  

Step 1:

-Must be age 18 -39
-Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO criteria) are eligible.
-Patients who have BCR-ABL fusion transcript determined by FISH or RT-PCR or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction.
-No prior therapy for ALL except for limited treatment (= 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine.
-No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys.
-Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience.
-ECOG PS must be 0-2
Step 2:
-Completion of remission induction therapy
-Patients with M2 marrow or better (0-25% blast cells) are eligible

Effective 06/14/22, enrollment to Pre-Registration (Step 0) is temporarily closed to accrual.

DTL Required- Physicians must sign the toxicity grids

Current Sites Credentialed: SJMH- (AA, Brighton, Canton, Chelsea), Sparrow, Saginaw, Livonia, St. John, GenesysHurley, LVHN, Holy Cross, St. Joseph Mercy Oakland

Eligibility Criteria: 

-Patients must have been diagnosed with CLL and have > 5000 B-cells per uL of peripheral blood at any point during the course of their disease.

-This blood submission is mandatory prior to registration/randomization to perform FISH centrally that will be used for stratification. It should be obtained as soon after pre-registration as possible.
-Patients must be diagnosed with CLL in accordance with 2018 IWCLL criteria [28] that includes all of the following:

• ?5x109 B lymphocytes (5000/?L) in the peripheral blood measured by flow cytometry at any point in the course of the disease.

• On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes.

• CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in >10% of cells must lack t(11;14) translocation by interphase cytogenetics.

-Patients must be intermediate or high-risk Rai stage CLL.

--Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly

--High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin <11 g/dL) or thrombocytopenia (platelet count <100 x 109/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia

-Patients must meet criteria for treatment as defined by 2018 IWCLL guidelines[16] which includes at least one of the following criteria: o Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)

--Massive (?6 cm below the costal margin), progressive or symptomatic splenomegaly

--Massive nodes (?10 cm) or progressive or symptomatic lymphadenopathy

--Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy

--Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)

--Constitutional symptoms, which include any of the following: ? Unintentional weight loss of 10% or more within 6 months

---Significant fatigue

---Fevers >100.5 degrees F for 2 weeks or more without evidence of infection

---Night sweats ?1 month without evidence of infection

-ECOG performance status 0-2

*Effective 11/15/23, Step 0 (Pre-Registration) to Cohort 1 is Permanently Closed. *Effective 11/15/23, Step 1 (Registration) to Cohort 1 is Permanently Closed.  *Effective 11/15/23, Step 0 (Pre-Registration) to Cohort 2 is Re-Activated. *Effective 11/15/23, Step 1 (Registration) to Cohort 2 is Re- Activated.  *DTL Required- Physicians must sign toxicity grid CREDENTIALING REQUIRED. Please check your site's credentialing status. CURRENT SITES CREDENTIALED: SJMH (AA, Brighton, Canton, Chelsea), Livonia, Genesys

If a BMB has already been performed prior to consent, there was no available aspirate, and the patient has circulating blasts, sites can just collect peripheral blood sample to send to study and not repeat the tap.

Cohort 1 and Cohort 2 Patients:

- Ph-negative, CD22-positive precursor B-cell acute lymphoblastic leukemia

- No active CNS leukemia

- No known or suspected testicular involvement by leukemia

- Not pregnant or nursing

- ECOG Performance Status: 0-2

- No unstable cardiac disease within 6 months of registration

- No LVEF < 45% or NYHA stage III or IV CHF

- No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal syncope, or chronic bradycardic states unless a permanent pacemaker has been implanted.

- Patients with known HIV infection, hepatitis B virus (HBV), and/or history of hepatitis C virus (HCV) are allowed if they meet specified criteria (see Section 3.3.4)

- No history of clinically relevant neurologic disorder

- No prior additional malignancy (see Section 3.3.5 for exceptions)

- No history of chronic liver disease including cirrhosis or SOS/VOD of the liver

- No uncontrolled infection

- Total bilirubin = 1.5 x ULN

- AST/ALT = 2.5 x ULN

- Calculated creatinine clearance = 40 mL/min

- QTcF = 470 msec

Cohort 1 Patients Only:

- Age = 60 years

- No prior therapy for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed therapy may be administered for no more than 14 days and must be completed = 24 hours before starting protocol therapy.

- No plan for allogeneic or autologous hematopoietic cell transplantation (HCT)

Cohort 2 Patients Only:

- Age = 18 years

- Relapsed or refractory disease in salvage 1 or 2

- No isolated extramedullary relapse

- Prior allogeneic HCT permitted. If prior allogeneic HCT, then patients must have completed transplantation = 4 months prior to registration, have no evidence of GvHD, and have completed immunosuppressive therapy = 30 days prior to registration.

- No prior treatment with CD22- or CD19-directed therapy. Prior treatment with rituximab must be completed = 14 days prior to registration. Prior treatment with other monoclonal antibodies must be completed = 6 weeks prior to registration.

- Prior treatment for ALL must be completed = 14 days prior to registration with the following exceptions: hydroxyurea, corticosteroids, 6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce circulating absolute lymphoblast count to = 10,000/µL or prevent complications related to ALL are allowed but must be completed = 24 hours prior to the start of protocol therapy.

- Resolution of acute non-hematologic toxicities of prior therapy to CTCAE v5.0 grade = 1

- Peripheral blood absolute lymphoblast count = 10,000/µL (treatment allowed as above to reduce blasts)

** Effective 09/28/2020, accrual of subjects with double hit lymphoma, regardless of age, is temporarily halted.

**ePRO training required prior to first patient enrollment.** 

*DTL Required- Physicians must sign toxicity grid

Sites Credentialed:  SJMH (Ann Arbor, Brighton, Canton, Chelsea), St. Mary's Livonia, LVHN, St. John, Holy Cross, Geneseys, Hurley

Eligibility Criteria:       

Documentation of Disease

• Pathologic diagnosis of Diffuse Large B-cell lymphoma (DLBCL) or High grade B-cell lymphoma (HGBCL)

• High grade B-cell lymphoma with translocations of MYC and BCL2 (Double Hit Lymphoma, DHL), or DLBCL or high grade B-cell lymphoma NOS with protein expression by IHC of both MYC (=40%) and BCL2 (=50%) in the

absence of dual translocations (Double Expressing Lymphoma, DEL). Local determination of FISH and IHC will be performed per standardized guidelines and will be acceptable for study entry.

• The diagnosis of DLBCL/HGBCL and assessment of DEL/DHL will be performed per standardized guidelines at local institutions and patients will be enrolled based on local determination. Given the heterogeneity in diagnostic work-up and interpretation, all local determinations will be followed by central confirmation in real time. Diagnostic slides and stains (or recuts/blocks) from all cases will be submitted to a central reference laboratory (Cleveland Clinic Laboratories). Immunostains will be reviewed or repeated (if unavailable or technically unsatisfactory) to confirm DE status. All DE cases will also be investigated for DH status, if not already performed. To exclude DH status, FISH for translocations of BCL2 (break apart probes), BCL6 (break apart probes), and MYC (break apart and IGH/MYC dual fusion probes) must be performed (either by referring site or at the central laboratory). Any missing information from the referring site will be supplemented by the central lab on

required submitted unstained slides or blocks. Cases submitted as DH will be accepted as such upon review of submitted laboratory report.

- No prior treatment for DLBCL/HGBCL is allowed with the exception of corticosteroids administered for palliation, or a single cycle of either R-CHOP or DA-EPOCH-R administered prior to enrollment. This single pre-registration cycle is being allowed to facilitate enrolling patients who required immediate initiation of therapy for rapidly progressing disease, or for patients where FISH or IHC results returned after initiation of chemotherapy rendered them protocol eligible.

-  Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.

-  Age = 18 years

- ECOG Performance Status 0-2

-  Required Initial Laboratory Values*:

Absolute Neutrophil Count (ANC) = 1,000/mm3

Platelet Count = 100,000/mm3

Creatinine = 1.5 mg/dL OR

Calc. Creatinine Clearance = 50 mL/min

Total Bilirubin = 2.0 mg/dL**

* Unless attributable to lymphoma

** Unless attributable to Gilbert’s disease

- Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional.

- Comorbid conditions

No active ischemic heart disease or congestive heart failure, and LVEF = 45%

No active HIV disease. Patients with history of HIV are eligible if they 1) have an undetectable viral load within the prior 6 months, or 2) have a detectable viral load with a CD4 count = 200

No known lymphomatous involvement of the CNS. A lumbar puncture or neuroimaging prior to study enrollment is not required in the absence of neurological signs or symptoms concerning for CNS involvement.

No active Hepatitis B or Hepatitis C infection. Patients with prior HBV exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of HCV are eligible if they have been treated for HCV and have an undetectable HCV viral load.

- Concomitant medications

Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to initiation of protocol therapy.

Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

**ePRO training required prior to first patient enrollment.** 

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status. 

CURRENT SITES CREDENTIALED: Trinity Health IHA Brighton (MI350) ONLY** 

***MI350 Brighton is on a 4-week wavier***

Eligibility Criteria:

A female of childbearing potential is a sexually mature female who:

1) has not undergone a hysterectomy or bilateral oophorectomy; or

2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

Documentation of Disease Histologically confirmed diagnosis of PTCL with <10% CD30 expression by immunohistochemistry in the following subtypes (by local review): Nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular Tcell lymphoma, PTCL-NOS, AITL, enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma

• Patients with expression of CD30 in ≥10% of the tumor (based on local immunohistochemistry review) regardless of histology will not be permitted.

• Patients with a diagnosis of other PTCL subtype histologies other than those specified in the inclusion criteria are excluded including large cell transformation of mycosis fungoides

• Patients will be stratified by presence or absence of TFH phenotype (i.e. diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of pathology. Determination of TFH phenotype can be defined by expression of two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by immunohistochemistry.

- Measurable, FDG avid disease as defined by the Lugano Criteria [26] (see Section 11.0).

- Prior Treatment No prior systemic therapy or radiation therapy for T-cell lymphoma (excluding corticosteroids)

- Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required.

- Age ≥ 18 years

- ECOG Performance Status ≤ 2  

Required Initial Laboratory Values:

-Platelet Count ≥ 75,000/mm3 (≥50,000/mm3 if secondary to bone marrow involvement from lymphoma per investigator assessment; the first 12 patients on each arm of the study must have platelets ≥75,000/mm3 regardless of bone marrow involvement)

-Absolute Neutrophil Count (ANC) ≥ 1,000/mm3 AST/SGOT and ALT/SGPT ≤ 3.0 x ULN* Calculated -Creatinine Clearance ≥ 30 mL/min by Cockcroft-Gault formula Total Bilirubin ≤ 2.0 x ULN**

* Except in subjects with documented liver involvement by lymphoma

** Except in cases of Gilbert’s Syndrome or documented liver or pancreatic involvement by lymphoma  Archival tissue must be available for submission

- Comorbid conditions

• Patients known to have HTLV 1/2 are excluded

• Patients with known central nervous system involvement are excluded

• No active viral infection with HIV, hepatitis B, or hepatitis C. Those who are seropositive (e.g. Hepatitis B core Ab positive) are permitted if they are negative by PCR. Those who are seropositive for hepatitis B and are negative for HBV DNA by PCR must receive concomitant hepatitis B directed antiviral therapy. Those who have hepatitis C Ab positivity who have completed curative therapy for hepatitis C with negative hepatitis C PCR are eligible.

• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.

• No active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment). Patients with EBV viremia related to their lymphoma are permitted.

• No concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted.

• Patients must have documented left ventricular ejection fraction of ≥ 45%.

• No significant active cardiac disease within the previous 6 months including: - New York Heart Association (NYHA) class III or IV congestive heart failure - Unstable angina or angina requiring surgical or medical intervention; and/or - Myocardial infarction

• No contraindication to any drug in the chemotherapy regimen, including neuropathy ≥ Grade 2

- Concomitant medications

- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. See Section 8.1 for more information.

Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. See Section 8.1 for more information.  

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: Trinity Health- SJMH ( Ann Arbor, Brighton, Canton, Chelsea) and Livonia, Genesys, Hurley

Eligibility Criteria:

3.2.1 Documentation of Disease

Histologic Documentation: Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or FISH as confirmed by the enrolling center.

Stage: Any stage allowed (stage I-IV)

3.2.2 Measurable disease as defined in Section 11.0.

Presence of measurable disease, defined as ≥ 1 nodal lesion that is > 1.5 cm in longest diameter or ≥ 1 extranodal lesion that is > 1 cm in longest diameter

 3.2.3 Prior Treatment

• Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days.

• No prior systemic treatment for mantle cell lymphoma.

• No prior radiation treatment for stage I MCL

• No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody

• No prior stem cell transplant 

3.2.4 Age ≥ 70 years OR age ≥ 60 to < 70 years with comorbidities precluding autoSCT including at least one of the following: a) cardiac EF <45%, b) diffusing capacity for carbon monoxide <60% predicted; c) creatinine clearance <70 but >30ml/min; d)Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score >6 (see Appendix IV) [13].

 3.2.5 ECOG Performance Status 0-2 (Appendix II)

 3.2.6 Required Initial Laboratory Values

 Absolute Neutrophil Count (ANC)   = ≥ 750/mm3 (without growth factor support within 7 days)

Platelet Count=  ≥ 75,000/mm3 (or ≥ 50,000/mm3 for patients with bone marrow involvement of lymphoma) without growth factor support or transfusion within 7 days

Creatinine Clearance = ≥ 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation (see Appendix I) or b) Measurement by nuclear medicine scan or 24 hour urine collection

Total Bilirubin= ≤ 1.5 x upper limit of normal (ULN) (unless documented Gilbert’s syndrome)

AST / ALT= ≤ 3 x ULN

 3.2.7 Comorbid conditions

• Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy

• No clinically significant cardiovascular disease including the following:

a. Unstable angina within 3 months before registration

b. New York Heart Association class III or IV congestive heart failure (see Appendix III)

c. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)

d. QTcF > 480 msecs based on Fredericia’s formula

e. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

• No active Hepatitis B or Hepatitis C infection. Patients with prior HBV exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of HCV are eligible if they have an undetectable HCV viral load.

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention 

• No history of stroke or intracranial hemorrhage within 6 months prior to registration

• No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills.

• Potential trial participants should have recovered from major surgery

• No vaccination with a live vaccine within 35 days prior to registration

• No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

**Effective 07/14/2020, Study is Closed to Accrual**

-Histologically confirmed diagnosis of symptomatic multiple myeloma. Relapsed disease is myeloma that has previously responded to prior therapy (MR or better) and subsequently progressed.
-Patients must have measurable disease defined as: Serum M-protein =1.0 g/dL (=0.5 g/dL for IgA myeloma) and/or urine M-protein =200 mg/24 hours and/or involved serum free light chain level =10 mg/dL AND an abnormal serum free light chain ratio and/or baseline marrow burden of myeloma of at least 30%.
-Must have previously treated symptomatic MM with at least 2 or more prior lines of systemic therapy
-Must have lenalidomide AND proteasome inhibitor-refractory disease
-Pomalidomide naïve and pomalidomide sensitive disease are allowed
-ECOG PS must be 0-2
-Patients cannot have CNS involvement, primary refractory MM, or primary or secondary plasma cell leukemia
-Patients must not have greater than grade 2 neuropathy

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

Effective 05/18/18- (STEP 0) is CLOSED to Accrual

Effective 10/15/18 (STEP 1) is CLOSED to Accrual
CURRENT SITES CREDENTIALED:
Genesys Hurley, Oakland, Saginaw, Sparrow, St. John, SJMH, St. Alphonsus, Livonia 
NOTE: MCRC is not participating in the advanced imaging sub-study.

*Eligibility clarification:  All patients with GBM regardless of the extent of resection are eligible; patients who are NOT resectable are also eligible.

Pre-registration Eligibility:
-Patients must have newly diagnosed WHO Grade IV intracranial glioblastoma or gliosarcoma. GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted. 
-Patients who have had a local MGMT testing that is unmethylated are not allowed to participate. 
-Patients will submit tissue for central pathology review and MGMT methylation status evaluation.

Registration Eligibility:
-Patients must have tumor MGMT promoter hypermethylation determined by central testing at MD Anderson.
-Patients must have confirmation by central pathology review of WHO Grade IV glioblastoma or gliosarcoma.
-ECOG PS must be 0-2
-Patients can have measurable and/or nonmeasurable disease. 
-Patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible. 
-Patients must have completed standard radiotherapy and concomitant TMZ therapy
-Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy, biologics, immunotherapy, radiation therapy.