Study to Assess the Efficacy and Safety of Umbralisib in Participants With Non-Follicular Indolent Non-Hodgkin's Lymphoma

May 29, 2023 updated by: TG Therapeutics, Inc.

A Phase 2 Study to Assess the Efficacy and Safety of TGR-1202 (Umbralisib) Monotherapy in Patients With Non-Follicular Indolent Non-Hodgkin's Lymphoma

This research study will evaluate the safety and efficacy of a study drug called Umbralisib (also known as TGR-1202) alone as a possible treatment for Waldenstrom's Macroglobulinemia that has come back or that has not responded to standard treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

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
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • TG Therapeutics Investigational Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • TG Therapeutics Investigational Trial Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • TG Therapeutics Investigational Trial Site
    • New York
      • New York, New York, United States, 10065
        • TG Therapeutics Investigational Trial Site

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of Waldenstroms Macroglobulinemia
  • Relapsed or refractory after at least one prior treatment regimen
  • Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

Exclusion Criteria:

  • Any major surgery, chemotherapy or immunotherapy within the last 21 days
  • Evidence of hepatitis B virus, hepatitis C virus or known HIV infection
  • Prior autologous stem cell transplant within 6 months of study entry

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Marginal Zone Lymphoma (MZL): Umbralisib
Participants with non-follicular indolent non-Hodgkin's lymphoma (iNHL) with MZL as the histology type received umbralisib, 800 milligrams (mg), orally, once daily (QD), until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Drug: Umbralisib
Oral Daily Dose
Other Names:
  • TGR-1202
Experimental: Waldenstrom's Macroglobulinemia (WM): Umbralisib
Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Drug: Umbralisib
Oral Daily Dose
Other Names:
  • TGR-1202

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) as Assessed by Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) and Consensus-Based 6th International Workshop on Waldenstrom's Macroglobulinemia (IWWM)
Time Frame: Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years
ORR for MZL=percentage of participants with complete response (CR)/partial response (PR). ORR for WM=CR/PR/very good partial response (VGPR)/minor response (MR). Response assessed per revised Lugano Classification for MZL &per IWWM for WM participants. Per Lugano criteria CR=complete disappearance of all evidence of disease & disease-related symptoms. PR=regression of measurable disease & no new disease sites. Regression=≥50% decrease in the sum of the products of the diameters (SPD) of index lesions, with no increase in size of other lymph nodes/liver/spleen.Per IWWM criteria CR=disappearance of serum monoclonal immunoglobulin M (IgM) protein by immunofixation with a normal serum IgM level. VGPR=reduction of monoclonal IgM protein >90% from baseline. PR=reduction of monoclonal IgM protein between 50-90% from baseline with regression of measurable disease. Regression defined in similar manner as Lugano Classification. MR=reduction of monoclonal IgM protein >25% but <50% from baseline.
Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years
Duration of Response (DOR)
Time Frame: From the first demonstration of response to umbralisib till disease progression/death (up to approximately 4.2 years)
DOR is defined as the time from documentation of a response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.
From the first demonstration of response to umbralisib till disease progression/death (up to approximately 4.2 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response (CR) Rate
Time Frame: Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

CR rate is defined as percentage of participants who achieved CR. CR was assessed using Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) for participants with MZL and Consensus-Based 6th IWWM for participants with WM.

Per Lugano Classification, CR= the complete disappearance of all evidence of disease and disease-related symptoms i.e., liver/spleen non palpable and normal in size and disappearance of nodules related to lymphoma.

Per IWWM criteria, CR=disappearance of serum monoclonal IgM protein by immunofixation with a normal serum IgM level, liver/spleen non palpable and normal in size and disappearance of nodes related to WM.
Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years
Progression-Free Survival (PFS)
Time Frame: From date of randomization until the date of first documented progression (up to approximately 4.2 years)

PFS is defined as the interval from Cycle 1 (1 cycle = 28 days) Day 1 to the earlier of the first documentation of definitive disease progression or death from any cause. Assessment of progressive disease (PD) was based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM.

Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 centimeters (cm) in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions, greatest transverse diameter (GTD) of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node is now ≥ 1.5 cm.

Per IWWM criteria participants, PD was defined as more than 25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.
From date of randomization until the date of first documented progression (up to approximately 4.2 years)
Time to Treatment Failure (TTF)
Time Frame: From first dose on Day 1 of Cycle 1 (28 days = 1 cycle) up to discontinuation of treatment (up to approximately 4.2 years)

TTF is defined as a composite endpoint measuring time from Cycle 1/Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. PD was assessed based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM.

Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 cm in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions, GTD of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node is now ≥ 1.5 cm.

Per IWWM criteria PD was defined as more than 25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.
From first dose on Day 1 of Cycle 1 (28 days = 1 cycle) up to discontinuation of treatment (up to approximately 4.2 years)
Number of Participants With at Least One Adverse Event (AE)
Time Frame: From first dose of study treatment up to end of study (up to approximately 4.2 years)
An AE is any untoward medical occurrence in a participant that does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
From first dose of study treatment up to end of study (up to approximately 4.2 years)

Collaborators and Investigators

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

Sponsor

TG Therapeutics, Inc.

Investigators

  • Study Chair: Bruce Cheson, MD, Lombardi Comprehensive Cancer Center

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 (Actual)

November 30, 2017

Primary Completion (Actual)

February 15, 2022

Study Completion (Actual)

February 15, 2022

Study Registration Dates

First Submitted

November 30, 2017

First Submitted That Met QC Criteria

November 30, 2017

First Posted (Actual)

December 6, 2017

Study Record Updates

Last Update Posted (Actual)

June 23, 2023

Last Update Submitted That Met QC Criteria

May 29, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TGR-1202-202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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