*Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
St. Alphonsus, St. John, SJMH 

**Submission of the treating investigators CV is required to order Bendamustine**

-Histologically confirmed follicular non-Hodgkin lymphoma, WHO classification grade 1, 2, or 3a (greater than 15 centroblasts per high-power field with centrocytes present)
-Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies. Fine-needle aspirates are not acceptable.
-Patients must have poor-risk disease defined by one of the following 2 criteria:
--greater than or equal to 3 risk factors by the Follicular Lymphoma International Prognostic Index
--2 risk factors by FLIPI and at least one bulky mass or lymph node greater than 6cm in size
-Measurable disease must be present either on physical examination or imaging studies. Any tumor mass > 1 cm is acceptable
-No known CNS involvement by lymphoma
-ECOG performance status 0-2
-No prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or radioimmunotherapy
-No corticosteroids are permitted, except for maintenance therapy for a nonmalignant disease or to prevent treatment-related ofatumumab reactions

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

CURRENT SITES CREDENTIALED:

Eligibility Criteria:

3.1.1 Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care.

3.1.2 Patients must have been treated by BCS or mastectomy with clear margins of excision*.

* Patients treated by BCS with focally positive margins for invasive breast cancer or DCIS (involving < 3 high power fields) are eligible if additional surgery is not possible, e.g. posterior margin positive and deep resection margin abuts the chest wall or anterior margin positive and superficial resection margin abuts the skin. Boost radiotherapy must be administered for positive margins as described above.

Post-mastectomy positive margins for invasive breast cancer and/or DCIS is not allowed.

 Multifocal disease (i.e. the presence of two or more foci of breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed.

3.1.3 Patients with T3N0 disease are eligible.

3.1.4 Patients with disease limited to nodal micrometastases are eligible.

3.1.5 Patients with nodal macrometastases (> 2 mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, > 2 mm)*.

3.1.6 Patients with nodal macrometastases (> 2 mm) treated by SLNB alone must have only 1-2 positive axillary nodes (macrometastases, > 2 mm)*.  

* Note patients with additional nodal micrometastases (> 0.2-2mm) or isolated tumour cells (≤ 0.2 mm) are eligible.

3.1.7 Patients must be ER ≥ 1% and HER2 negative on local testing  

3.1.8 Patients must have an Oncotype DX recurrence score ≤ 25 obtained from testing of breast tumour tissue from a core biopsy or from the surgical specimen.**, ***

** If the patient does not already have Oncotype DX recurrence score, specimen (unstained blocks or slides) must be sent to the Exact Sciences centralized laboratory in Redwood City, California. For Canadian sites, see the MA.39 website https://www.ctg.queensu.ca/trials/breast/ma39 and for US sites, see the CTSU website for the CCTG MA.39 trial for instructions on ordering Oncotype DX test.

*** Oncotype DX testing must be performed on a core biopsy PRIOR to commencement of neoadjuvant endocrine therapy. See ineligibility criterion 3.2.8 for further details on the duration of neoadjuvant endocrine therapy.

3.1.9 Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted. Where tissue exists but local centre regulations prohibit submission of blocks of tumour tissue, the approval of the CCTG must be sought prior to randomization of the first patient to allow cores (two 2 mm cores of tumour from the block) and slides (20 x 5 micron thick unstained slides) of representative tumour tissue to be substituted. Where tumour tissue is available, failure to submit any tissue samples will result in the patient being considered ineligible.

3.1.10 Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted.

3.1.11 Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT.

3.1.12 Patients may or may not have had adjuvant chemotherapy.  

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

INCLUSION CRITERIA:

1. Participant must be ? 18 years at the time of screening.
2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
3. Provision of a tumour tissue sample obtained prior to CRT
4. Documented tumour PD-L1 status ? 1% by central lab
5. Documented EGFR and ALK wild-type status (local or central).
6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy
7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
9. WHO performance status of 0 or 1 at randomization
10. Adequate organ and marrow function

EXCLUSION CRITERIA:

1. History of another primary malignancy, except for:

   • Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence.
   • Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease .
   • Adequately treated carcinoma in situ, including Ta tumors without evidence of disease.
2. Mixed small cell and non-small cell lung cancer histology.
3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
6. Participants with ? grade 2 pneumonitis from prior chemoradiation therapy.
7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (? Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis
8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
9. Active EBV infection, or known or suspected chronic active EBV infection at screening
10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Inclusion Criteria:

1. Capable of giving signed informed consent prior to any study procedure.
2. Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.

3. Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:

   (a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.

4. Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
5. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Predicted life expectancy of ? 12 weeks.
8. Adequate organ and bone marrow function
9. Body weight of ? 35 kg.
10. Sex and Contraceptive Requirements

Exclusion Criteria:

1. Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ? 2 or an average HER2 copy number ? 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.
2. Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
3. CNS metastases or CNS pathology including: epilepsy, seizures, aphasia, or stroke within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.
4. Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
5. Persistent toxicities (CTCAE Grade ? 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
6. Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).

*Check eligible studies list in document library.
-All patients (pediatric and adults) screened for selected NCORP trials supported by the Division of

Cancer Prevention (DCP). These trials include symptom and toxicity management, prevention,

screening, post-treatment surveillance and comparative effectiveness. Cancer care delivery clinical

trials will be included if the primary aim focuses on a patient intervention. A screened patient will be

defined as one meeting the following minimum eligibility criteria per the protocol being screened for:-

--Cancer diagnosis including stage and histology or pre-malignancy
--Age range specified in the protocol for which the patient is being screened
--Indication for the study intervention (e.g., symptom, toxicity)

Pre-Registration Eligibility:

-Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or FISH
-Patients must have measurable disease
-Patient must have no CNS involvement
-ECOG performance status 0-2
-No prior therapy for MCL, except  2 weeks of steroid therapy for symptom control or local RT for symptom control if there is measurable disease outside the RT portal

Registration Eligibility:
-ECOG PS between 0-2
-CR, PR, or SD after step 1

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

Pre-Registration Eligibility:
-Histologically confirmed DLBCL expressing CD20 antigen. (Patients with transformed lymphoma, with known primary mediastinal large B-cell lymphoma, or with composite lymphoma in the diagnostic tissue are excluded. Patients with DLBCL in primary diagnostic tissue but a bone marrow that shows low grade or indeterminate lymphoma are eligible.
-Patients must have stage II bulky disease, stage III, or stage IV.
-ECOG performance status must be 0-2
-Patients must be previously untreated and not receiving any other agent that would be considered as a treatment for the lymphoma. For patients with severe systemic symptoms, compressive disease, or rapidly progression symptomatic adenopathy, there is an allowance with up to 1mg/kg/day of prednisone, or equivalent, for a max of 7 days prior to beginning treatment.
-Patients must not have any known CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
-Must not have history of RT to greater than or equal to 25 % of the bone marror for other diseases or history of anthracycline therapy.
-Patients must not be receving erythroid stimulating agents.

Registration Eligibility:
-Must continue to meet pre-registration eligibility.
-Patients must have measurable disease.
-IPI must be 2 or greater.

1.0) Histologic or cytologic NSCL, pts must have recurrent dz after prior RT or surgery OR Stage IV dz OR Stage IIIB w/pleural or pericardial effusion seen on CXR or CT
2.0) Stage IV pt's with brain mets are eligible if brain mets are stable after txment with RT or surgery
3.0) Must have ECOG PS of ****2*****
4.0) Prior RT okay as long as it's not the only site of msble or evlble dz and the pt has recovered
5.0) No prior Chemo

ARM A  WILL BE CLOSED TO ACCRUAL EFFECTIVE APRIL 4, 2014 AS IT WILL HAVE MET ITS ACCRUAL GOAL

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

Criteria
DISEASE CHARACTERISTICS:

?Diagnosis of melanoma of a cutaneous origin or unknown primary

?No ocular melanoma or melanoma of mucosal origin
?Stage IIIB, IIIC, or IV (M1a or M1b) disease

?Patients with stage IV melanoma must have normal LDH and distant skin, subcutaneous, lymph node, or lung metastases
?No other visceral metastases allowed
?Disease that has been completely resected with negative margins on resected specimens within the past 12 weeks

?Disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization

?Imaging studies must include a total body PET-CT scan (with or without brain) and brain MRI or CT (if MRI is contraindicated) (if PET-CT cannot be done, CT scan of neck, chest, abdomen, and pelvis should be done)
?Patients rendered free of disease by non-surgical means not allowed
?Disease recurrence after adequate surgical excision of original primary cutaneous melanoma allowed provided one of the following criteria are met:

?Recurrence in a regional lymph node basin after a prior complete lymph node dissection

?Relapsed disease must be completely surgically resected with free margins
?Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal, or lung metastases that are completely surgically resected with free margins
?Recurrence in a regional lymph node basin

?Relapsed disease must be completely surgically resected with free margins
PATIENT CHARACTERISTICS:

?ECOG performance status 0-1
?WBC ? 3,000/?L
?ANC ? 1,500/?L
?Platelet count ? 100,000/?L
?Hemoglobin ? 10 g/dL
?Serum creatinine ? 1.8 mg/dL
?AST and ALT ? 2.5 times upper limit of normal (ULN)
?Serum bilirubin 2 times ULN ( 3 mg/dL in case of Gilbert syndrome)
?Not pregnant or nursing
?Negative pregnancy test
?Fertile patients must use adequate method of contraception throughout the study and for up to 26 weeks after the last dose of high-dose recombinant interferon alpha-2b (HDI)
?No active infection requiring concurrent treatment with parenteral antibiotics
?None of the following:

?Other significant medical, surgical, or psychiatric conditions
?Requirement for any medication or treatment that, in the opinion of the investigator, may interfere with compliance, make the administration of ipilimumab or HDI hazardous, or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
?No documented history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, or diverticulitis

?History of diverticulosis allowed
?No autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids or continuous use of topical steroid creams or ointments or ophthalmologic steroids

?History of occasional (but not continuous) use of steroid inhalers allowed
?None of the following:

?History of symptomatic autoimmune disease

?Rheumatoid arthritis
?Systemic progressive sclerosis (scleroderma)
?Systemic lupus erythematosus
?Sjögren syndrome
?Autoimmune vasculitis (e.g., Wegener granulomatosis)
?Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis)
?Other CNS autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
?Autoimmune hypothyroid disease or type 1 diabetes allowed provided replacement therapy is administered
?Not incarcerated or compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
?No other current malignancies except any prior in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, basal or squamous skin cancer, or other malignancies for which the patient has been disease free for > 5 years
?No active or chronic infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)

?Patients must have negative testing for HIV, HBV, and HCV within the past 4 weeks
PRIOR CONCURRENT THERAPY:

?See Disease Characteristics
?No prior adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after resection
?At least 30 days since prior radiotherapy, including after surgical resection
?No prior or concurrent anti-CTLA4 monoclonal antibodies, CTLA-4 inhibitor or agonist, CD137 agonist, or prior interferon-?
?At least 4 weeks since prior aldesleukin (IL-2), anti-tumor vaccine, or chemotherapy given before randomization
?No infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within the past 4 weeks
?No concurrent systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids

?Occasional but not continuous use of steroid inhalers allowed
?Systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone), continuous use of topical steroid creams or ointments, or ophthalmologic steroids within the past 2 weeks allowed provided, in judgment of the treating physician investigator, that the patient is not likely to require resumption of treatment with these classes of drugs during the study
?Replacement doses of steroids for patients with adrenal insufficiency allowed
?No concurrent chemotherapy or radiotherapy
?No other concurrent anticancer or investigational agent

STUDY DRUG: Provided - Interferon alpha-2b (pg 16)
1) Melanoma of cutaneous origin (see pg 2 for elig criteria - staging)
2) Only initial presentation of primary melanoma eligible
3) Must complete all primary therapy & rando'ed within 84 days of wide excision
4) No prior RT or chemotx
5) ECOG PS: 0-1