-Patients must be candidates for cytoreductive surgery and consent to have their surgical treatment determined by randomization
-Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent.
-Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma NOS
-Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles)
-Patients must have a treatment-free interval without clinical evidence of progressive disease lasting at least 6 months.
-Patients must have clinically evident recurrent disease.
-GOG PS must be 0-2
-Patients must not have received mor than one previous regimen of chemotherapy
-Patients must not be receiving concurrent immunotherapy or radiotherapy
-Patients who have received prior RT to any portion of the abdominal cavity or pelvis are excluded.
-Patients who have already undergone secondary cytoreduction for recurrence are excluded
-Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than gyn) are excluded

-Patients initially diagnosed with low-grade serous ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas OR
-Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas
-Patients must have documented low-grade serous carcinoma; confirmation must occur by prospective pathology review prior to study entry; the prospective pathology review must be done on tissue from the recurrent carcinoma
-At least 4 weeks must have elapsed since any major surgery
-All patients must have measurable disease
-Patients must have recurred or progressed following at least one platinum-based chemotherapy regimen
-Patients may have received an unlimited number of prior therapy regimens
-Patients may not have received all of the five choices in the "standard therapy" arm
-Patients must have a GOG performance status of 0 or 1
-If letrozole is selected as the control therapy, patients must be postmenopausal
-No patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
-If patients have had a potential index lesion radiated, it must have progressed post radiation therapy to be used as a measurable eligibility lesion
-Patients may not have received prior MEK, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor therapy
-Patients with known leptomeningeal or brain metastases or spinal cord compression should be excluded from this clinical trial

-Patients must have pathologically proven non-small cell lung cancer (all histologic types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV as defined in Section 4.0 , or recurrent. The primary diagnosis of non-small cell lung cancer should be established using the current WHO/IASLC-classification of Thoracic Malignancies.
-Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment.
-Screening at progression on prior treatment:

--To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (Stages I-IV) and must have progressed during or following their most recent line of therapy.

-Pre-Screening prior to progression on current treatment:

--To be eligible for pre-screening, current treatment must be for Stage IV or recurrent disease and patient must have received at least one dose of the current regimen. Patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab). Patients on first-line treatment are eligible upon receiving Cycle 1, Day 1 infusion.

Note: Patients will not receive their sub-study assignment until they progress and the LungMAP Notice of Progression is submitted.
-Patients must have adequate tumor tissue available, defined as ? 20% tumor cells and ? 0.2 mm3 tumor volume.

• The local interpreting pathologist must review the specimen.

• The pathologist must sign the LungMAP

Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration.
-Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling, PD-L1, and c-MET IHC (see Section 15.2). If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12 unstained slides plus an H&E stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment.
-Patients must agree to have any tissue that remains after testing retained for the use of sub-study Translational Medicine (TM) studies at the time of consent the patient is enrolled in.
-Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/pre-screening.
-Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within 28 days prior to Step 1 registration.

*DTL Required- Physicians must sign toxicity grid

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

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

Eligibility Criteria:

 3.3.1 Documentation of Disease

Patients must have a morphologically-confirmed diagnosis of MDS with an IPSS-R score ≥4 (See Appendix VI for IPSS-R scoring) [2]. Patients must have a detectable pathogenic IDH2 mutation based on the NCI Myeloid Panel. 

3.3.2 Prior Treatment 

-No prior treatment with DNA methyltransferase inhibitors (ASTX727, azacitidine, or decitabine). 

-Prior treatment with growth factors (ESA, g-CSF, TPO agonist), lenalidomide or luspatercept is allowed with a maximum limit of 1 month of exposure.

-Patients with therapy-related MDS are allowed.

3.3.3 Age ≥ 18 years

3.3.4 ECOG Performance Status ≤ 2

3.3.5 Required Initial Laboratory Values

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

-AST (SGOT)/ALT (SGPT) ≤ 3.0 x upper limit of normal (ULN)

-GFR ≥ 30 mL/min/1.73m2**  

 *Unless elevated due to Gilbert’s syndrome. In patients with Gilbert’s syndrome, if the total bilirubin is ≤ 3.0 × ULN, then they are eligible for enrollment.

**To be calculated using Cockroft Gault formula.

3.3.6 Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done as part of screening lab work prior to registration is required.

3.3.7 Comorbid Conditions

-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.

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

-Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

-Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load 

**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: Trinity Health IHA ( Ann Arbor, Brighton, Canton, Chelsea) and Livonia, Genesys, Hurley, Lehigh

Eligibility Criteria:

3.1.1 Patient must be ≥ 60 years of age or adults ? 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status, age >75 years), organ dysfunction, or disease biology.

3.1.2 Patient must have a morphologically confirmed diagnosis of AML according to the WHO 2016 classification excluding APL with PML\u0002RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11.

3.1.3 Patient must have no prior therapy for AML with the exception of hydroxyurea and all-trans retinoic acid (ATRA), or leukapheresis. Patients with cytarabine-based emergency therapy prior to the start of therapy on this trial are eligible.

3.1.4 Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors.

3.1.5 Patient must have the FLT3-ITD or D835 mutation based on MyeloMATCH Master Screening and Reassessment Protocol (MSRP) 

3.1.6 Patient must be assigned to this protocol by the myeloMATCH MSRP.

3.1.7 Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.

A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Patient of child bearing potential? ______ (Yes or No)

Date of blood test or urine study: ___________ 

3.1.8 Patient of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for 30 days after the last dose of Venetoclax for all patients and for 6 months after the last dose of Gilteritinib for patients of childbearing potential and for 4 months after the last dose of Gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends.

3.1.9 Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision\u0002making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. 

3.1.10 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial.

3.1.11 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

3.1.12 Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

3.1.13 Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug.

3.1.14 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. 

 **PLEASE SEE THE 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: Trinity Health SJMH IHA (Brighton, Ann Arbor, Canton, Chelsea) Livonia, Genesys

Eligibility Criteria: 

5.1. Disease Related Criteria

a. Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have disease with a detectable IDH2 mutation based on central testing through the MYELOMATCH and be assigned to this clinical trial via MATCHBox prior to registration to this study. Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH. See Section 18.5 for details.

b. Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by having ≥ 20% blasts in the bone marrow and/or peripheral blood, excluding acute promyelocytic leukemia (APL) with PML-RARA.

5.2. Prior/Concurrent Therapy Criteria

a. Participants must not be receiving or planning to receive any other investigational agents while on protocol therapy.

b. Participants must not have received prior therapy for AML or MDS and/or MPN with the exception of hydroxyurea, all-trans retinoic acid (ATRA), colony\u0002stimulating factors, erythropoiesis-stimulating agents, immunosuppressive therapy, intrathecal chemotherapy, a single dose of cytarabine for cytoreduction, and/or leukapheresis.

c. Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide are allowed. Participants may receive hydroxyurea prior to treatment assignment on this substudy for cytoreduction but must agree to discontinue hydroxyurea prior to beginning treatment on this substudy.

1. WBC must be < 25 x 109 /L. Hydroxyurea, leukapheresis, and cytarabine < 1 g/m2 are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped prior to initiation of protocol therapy. 

5.3. Clinical/Laboratory Criteria

a. Participants must be ≥ 60 years old; OR must be ≥ 18 years old and considered not eligible for cytarabine-based induction therapy.

b. Participants must have Zubrod Performance Status of 0-3 as determined by a history and physical (H&P) exam completed within 14 days prior to registration (see Section 10.6).

c. Participants must have a complete medical history and physical exam within 14 days prior to registration. 

d. Participants must have adequate organ function as defined below within 14 days prior to registration:

- total bilirubin ≤ 1.5x institutional upper limit of normal (ULN) unless history of Gilbert’s syndrome. Participants with history of Gilbert’s syndrome must have total bilirubin ≤ 3 x institutional ULN.

- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN, unless considered to be elevated due to disease involvement.

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