This phase II MATCH treatment trial identifies the effects of crizotinib in patients whose cancer has a genetic change called ALK rearrangement. Crizotinib may stop the growth of cancer cells by blocking the ALK protein which may be needed for cell growth. Researchers hope to learn if crizotinib will shrink this type of cancer or stop its growth.

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive crizotinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Inclusion Criteria:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
• Patients must have an ALK rearrangement as defined via the MATCH Master Protocol
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)

Exclusion Criteria:

• Patients must not have non small cell lung cancer or anaplastic large cell lymphoma (ALCL)
• Patients with a history of interstitial lung disease or pneumonitis are excluded
• Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition
• Patients must not have had prior ALK-targeted inhibitors, including crizotinib, ceritinib, alectinib, AP26113, TSR-011, X-396, RXDX-101, CEP-37440, PF-06463922
• Patients must not have had brain metastases unless 1) treated and neurologically stable for at least 2 weeks, or 2) untreated, asymptomatic, and treatment is not indicated. Steroids are permitted if doses are stable (or tapering) for 2 weeks prior to study enrollment
• Patients using drugs or foods that are known potent CYP3A4 inhibitors or inducers will be excluded