A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL

A Multi-center Phase I/Ib Study Evaluating the Efficacy and Safety of the Novel PI3k Delta Inhibitor TGR-1202 in Combination With Ibrutinib in Patients With Select B-Cell Malignancies

This research study will be evaluating the safety and efficacy of a study drug called TGR-1202 in combination with a known drug ibrutinib, also known as Imbruvica, as a possible treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Mantle Cell Lymphoma (MCL) that has come back or that has not responded to standard treatment.

This research study is a Phase I and Ib combination clinical trial, which aims to both evaluate the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drug to evaluate in later clinical trials. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved TGR-1202 in the United States for use in MCL/CLL/SLL cancers.

TGR-1202 is a newly developed drug that may stop cancer cells from growing based on recent laboratory experiments. The results from these experiments suggest this drug may help to kill cancer cells when coupled with ibrutinib. In this research study, the safety and tolerability of TGR-1202 is being investigated to determine the highest dose that can safely be used in combination with ibrutinib. The study is also aimed to evaluate whether TGR-1202 has any effect on tumor growth (nodal response), and to determine the overall repsonse rate and duration of response in patients with CLL/SLL or MCL

Inclusion Criteria:

• Confirmed diagnosis of Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL)
• Adequate organ system function ( Absolute neutrophil count, Platelets,Bilirubin, Platelets, Aspartate transferase ,Alanine aminotransferase, Creatinine Clearance)
• Eastern Cooperative Group (ECOG) Performance status ≤ 2
• Ability to swallow and retain oral medication
• Female patients: must have negative serum pregnancy test at study screening/ all male partners must consent to use a medically acceptable method of contraception
• Willingness and ability to comply with trial and follow-up procedures, and give written informed consent

Exclusion Criteria:-

• Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) within 3 weeks of Cycle 1/Day 1,

• Autologous hematologic stem cell transplant within 3 months of study entry.

• Allogeneic hematologic stem cell transplant within 12 months.

  • Post-allo patients must not have active graft versus-host disease

• Evidence of active Hepatitis B,Hepatitis C or HIV infection.

• Active central nervous system involvement by lymphoma

• Requires treatment with strong CYP3A4/5 inhibitors

• Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

• QTcF >470 msec (QT interval, Fredericia calculation)

• Angina not well-controlled by medication

• Poorly controlled or clinically significant atherosclerotic vascular disease

• Presence of other active cancers, or history of treatment for invasive cancer within the past 2 years.

• Require warfarin for anticoagulation

• Women who are pregnant or lactating