Clinical trial NCT02268851: A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Mantle Cell Lymphoma
Keywords: Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: TG Therapeutics, Inc.
name: The Leukemia and Lymphoma Society
name: Blood Cancer Research Partnership
First posted: 2014-10-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
timeFrame: Participants were assessed every week or more often as needed during Cycle 1 or more often for up to 28 days to assess Dose-limiting toxicities (DLTs) during Phase I
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter
measure: Rate of Nodal Partial Response With Lymphocytosis (nPR)
timeFrame: At baseline, End of Cycle 2, End of Cycle 5, End of Cycle 9, End of Cycle 14 and approximately q6 months until C26, then investigator discretion thereafter
measure: Median Progression-Free Survival (PFS)
timeFrame: Disease will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter. In long-term follow-up, survival will be followed every 3 cycles up to 2 years.
measure: Median Duration of Overall Response (DOR)
timeFrame: Disease response will be evaluated at baseline, cycle 1 day 1,8,15,22 and cycle 2 day 1,15, and cycle 3-6 on day1, and every 2 cycles until cycle 12, then every 3 cycles thereafter.
Other outcomes:
Locations:
city: Monterey
country: United States
facility: Pacific Cancer Care
state: California
city: Hartford
country: United States
facility: St. Francis Hospital and Cancer Center
state: Connecticut
city: Brewer
country: United States
facility: Eastern Maine Medical Center/ Northern Light Cancer Care
state: Maine
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconness Medical Center
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Matthew Davids, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davids MS, Kim HT, Nicotra A, Savell A, Francoeur K, Hellman JM, Bazemore J, Miskin HP, Sportelli P, Stampleman L, Maegawa R, Rueter J, Boruchov AM, Arnason JE, Jacobson CA, Jacobsen ED, Fisher DC, Brown JR; Blood Cancer Research Partnership of the Leukemia and Lymphoma Society. Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1-1b study. Lancet Haematol. 2019 Jan;6(1):e38-e47. doi: 10.1016/S2352-3026(18)30196-0. Epub 2018 Dec 14.