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

January 5, 2024 updated by: Matthew S. Davids, MD, Dana-Farber Cancer Institute

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / 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

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Monterey, California, United States, 93940
        • Pacific Cancer Care
    • Connecticut
      • Hartford, Connecticut, United States, 06105
        • St. Francis Hospital and Cancer Center
    • Maine
      • Brewer, Maine, United States, 04412
        • Eastern Maine Medical Center/ Northern Light Cancer Care
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconness Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CLL

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.

  • Each Cycle = 28 days
  • TGR-1202 (oral): Starting on Day 1 administered daily.
  • Ibrutinib (oral): Starting on Day 1 administered daily.
Drug: TGR-1202
Capsules taken whole daily with water and with food
Other Names:
  • RP5264
  • Umbralisib
Drug: Ibrutinib
Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges
Other Names:
  • PCI-32765
  • Imbruvica
  • CRA-032765
Experimental: MCL

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.

  • Each Cycle = 28 days
  • TGR-1202 (oral): Starting on Day 1 administered daily.
  • Ibrutinib (oral): Starting on Day 1 administered daily.
Drug: TGR-1202
Capsules taken whole daily with water and with food
Other Names:
  • RP5264
  • Umbralisib
Drug: Ibrutinib
Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges
Other Names:
  • PCI-32765
  • Imbruvica
  • CRA-032765

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
Time Frame: 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
To assess the safety of TGR1202 in combination with ibrutinib relapsed or refractory CLL or MCL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 4 anemia; Grade 4 neutropenia lasting >7 days (while receiving growth factor support); Grade 4 thrombocytopenia lasting > 7 days; Grade ≥3 febrile neutropenia; and Grade ≥3 thrombocytopenia with Grade >2 hemorrhage;Grade ≥ 3 non-hematologic toxicity unresponsive to standard supportive care measure with the exception of asymptomatic Grade ≥3 lab abnormalities that resolve to ≤ Grade 1 or baseline within 7 days;treatment delay of ≥14 days due to unresolved toxicity; and non-hematologic toxicity of Grade 2 (at any time during treatment) that, in the judgment of the Investigators, Study Chair, and the Medical Monitor, is dose-limiting.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response
Time Frame: 2 Years
2 Years
Overall Response Rate
Time Frame: 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
Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008) by Lugano Criteria ( Cheson et al,.24) for MCL
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
Rate of Nodal Response With Lymphocytosis (nPR)
Time Frame: 2 years
2 years
Rate of Progression Free Survival
Time Frame: 2 Years
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

TG Therapeutics, Inc.
The Leukemia and Lymphoma Society
Blood Cancer Research Partnership

Investigators

  • Principal Investigator: Matthew Davids, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

May 1, 2018

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

October 16, 2014

First Submitted That Met QC Criteria

October 16, 2014

First Posted (Estimated)

October 20, 2014

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-396
  • TGR-IB-105 (Other Identifier: TG Therapeutics)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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