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

NCT ID: NCT02268851

Last Updated: 2024-11-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2022-10-31

Brief Summary

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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

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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

Conditions

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Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Mantle Cell Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

TGR-1202

Intervention Type DRUG

Capsules taken whole daily with water and with food

Ibrutinib

Intervention Type DRUG

Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges

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.

Group Type EXPERIMENTAL

TGR-1202

Intervention Type DRUG

Capsules taken whole daily with water and with food

Ibrutinib

Intervention Type DRUG

Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges

Interventions

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TGR-1202

Capsules taken whole daily with water and with food

Intervention Type DRUG

Ibrutinib

Capsules taken whole with water- Do not consume fish oil, vitamin E, grapefruit, or Seville oranges

Intervention Type DRUG

Other Intervention Names

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RP5264 Umbralisib Imbruvica CRA-032765 PCI-32765

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TG Therapeutics, Inc.

INDUSTRY

Sponsor Role collaborator

The Leukemia and Lymphoma Society

OTHER

Sponsor Role collaborator

Blood Cancer Research Partnership

OTHER

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Matthew S. Davids, MD

Principal Investigators

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Matthew Davids, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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Pacific Cancer Care

Monterey, California, United States

Site Status

St. Francis Hospital and Cancer Center

Hartford, Connecticut, United States

Site Status

Eastern Maine Medical Center/ Northern Light Cancer Care

Brewer, Maine, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconness Medical Center

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 30558987 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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TGR-IB-105

Identifier Type: OTHER

Identifier Source: secondary_id

14-396

Identifier Type: -

Identifier Source: org_study_id

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