An Open Label Navigational Investigation of Molecular Profile-Related Evidence Determining Individualized Cancer Therapy for Patients With Incurable Hematologic Malignancies (I-PREDICT Heme)

Inclusion Criteria:

* Patients with incurable hematologic malignancies with ≥50% 2-year cancer-associated mortality.
* Patients with relapsed/refractory hematologic malignancies, irrespective of 2-year mortality, who, in the opinion of the investigator, have no treatment option expected to yield significant clinical benefit.
* Patients with a rare tumor histology (i.e., fewer than 6 cases per 100,000 per year) with no approved therapies.
* Patients must have measurable disease for malignancies: defined as at least one lesion that can be accurately measured in at least one dimension with spiral CT scan, PET-CT, MRI, or calipers by clinical exam. Or presence of hematologic abnormalities with or without bone marrow involvement.
* Patients must have evaluable tissue/blood with adequate tumor content/purity for testing as specified by the molecular profiling lab. This will be obtained during the standard of care tumor diagnosis and tumor staging evaluation.
* Age ≥ 18 years.
* ECOG Performance Status 0-2.
* New York Heart Association (NYHA) Functional Classification I-II.
* Adequate organ function that reasonably allows for safe administration of therapy.
* At the time of treatment, patients should be off other anti-tumor agents for at least 5 half-lives of the agent or 2 weeks from the last day of treatment, whichever is shorter, so long as there is recovery from clinically significant side effects from previous therapy to less than or equal Grade 1.
* Able to swallow and/or retain oral medication, if needed.
* Ability to understand and the willingness to sign a written informed consent.
* Female patients of childbearing potential must agree to use at least one form of contraception during the study.

Patients must have at least one of the following for a diagnosis/disease status:

1. Advanced symptomatic disease
2. Medically unfit for standard therapy
3. Disease where no conventional therapy leads to a survival benefit \> 3 months in the respective cohort and line of therapy for which the patient is otherwise eligible
4. Actionable biologically informed targets determined by certified genomic profiling, immunophenotyping or other clinically validated techniques.

Exclusion Criteria:

* Severe or uncontrolled medical disorder that would, in the investigator's opinion, confound study analyses of treatment response or preclude the patient from safely receiving treatment (i.e. substance abuse or psychiatric illness/social situations that would limit compliance with study requirements).
* Pregnancy, breast-feeding women or any patient with childbearing potential not using adequate pregnancy prevention.
* Inadequate end organ function that would preclude safe administration of anti-neoplastic therapy; including hepatic dysfunction (LFTs \> 5 x normal limit, total bilirubin \> 3 and Cr \> 3 x normal limit or GFR \< 20 cc/min, or symptomatic heart failure (EF \< 20%), except when organ function impairment is a consequence of underlying malignancy and there is a reasonable expectation for improvement following initiation of appropriate therapy.
* Uncontrolled infections or sepsis. Patients with chronic viral infections (including HIV, HBV/HCV) that are controlled with appropriate concurrent therapy are allowed to participate in the study, provided ongoing compliance with antiviral therapy can be reasonably expected throughout the duration of the study. Patients with acute infections must start appropriate anti-microbial therapy and demonstrate stabilization of infection prior to study initiation.