TGR1202 in Relapsed and Refractory Follicular Lymphoma

Sponsor
Columbia University (Other)
Overall Status
Terminated
CT.gov ID
NCT03178201
Collaborator
TG Therapeutics, Inc. (Industry)
5
1
1
34.3
0.1

Study Details

Study Description

Brief Summary

The primary objective is to determine the overall response rate (ORR) of TGR-1202 in R/R FL.

Secondary Objectives

  • Determine the genetic and other novel biological markers that may be predictive of response or resistance to TGR-1202 in patients with relapsed or refractory FL.

  • Describe the Progression Free Survival (PFS), Duration of Response (DoR) after treatment with TGR-1202.

  • Describe the number of dose delays and dose reductions and other safety profile.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is an open label, phase II study of TGR-1202 in patients with relapsed or refractory (R/R) Grade 1, 2, or 3A follicular lymphoma (FL). FL is the most common subtype of indolent lymphoma. The prognosis of FL depends on the histologic grade, stage, treatment and age of the patient. More recently, efforts have been made to find novel regimens for the treatment of relapsed FL that do not contain non-specific cytotoxic agents.

One of the important goals of this phase II study is to discover novel genetic, biochemical, and immunological markers that are associated with the response and safety of TGR-1202 in patients with FL. TGR-1202 blocks PI3K, a signal that is required for cancer to grow.

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Study of the Phosphoinositide-3-Kinase-Delta Inhibitor TGR-1202 in Patients With Relapsed or Refractory Follicular Lymphoma
Actual Study Start Date :
Aug 20, 2017
Actual Primary Completion Date :
Jun 30, 2020
Actual Study Completion Date :
Jun 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: TGR-1202

Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202.

Drug: TGR-1202
Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
Other Names:
  • formerly as RP5307
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate [Up to 3 years]

      The sum of patients with partial responses and complete responses.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) After Treatment With TGR-1202 [Up to 3 years]

      The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

    2. Duration of Response (DoR) After Treatment With TGR-1202 [Up to 3 years]

      The time of initial response until documented tumor progression.

    3. Number of Dose Delays [Up to 3 years]

      The number of instances of patients having a dose of study drug delayed 1 or more days.

    4. Number of Dose Reductions [Up to 3 years]

      The number of instances of patients having to reduce the dosage of study drug based on specified toxicities.

    5. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Up to 3 years]

      Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] broken down by adverse event and CTCAE v4.0 grade of each event.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically proven diagnosis of grade 1, 2, or 3A FL.

    • Relapse following first line immunotherapy or chemoimmunotherapy. There is no upper limit to the number of therapies received prior to study entry. Prior therapies may include high-dose therapy with autologous stem cell rescue.

    • Measurable Disease according to the Lugano classification.

    • Lymphoma that is amenable to safe pre-treatment and post-treatment biopsy. The safety of the procedures will be determined by the treating physician and the surgeon in consultation with the PI, and in accordance with standard clinical practice. Acceptable sites of disease include, for example: (1) palpable tumor mass that is accessible under direct visualization or sonogram, (2) non-palpable tumor tissue that is accessible for biopsy under computed tomography (CT) or sonogram guidance, (3) bone marrow.

    • Age >18 years

    • Eastern Cooperative Oncology Group (ECOG) performance status <2

    • Patients must have adequate organ and marrow function as defined below:

    1. absolute neutrophil count >1,000/microliter

    2. platelet count ≥50,000/microliter

    3. bilirubin <1.5 x institutional upper limit of normal

    4. aspartate transaminase (AST, SGOT)/alanine transaminase (ALT, SGPT) <3.0 x institutional upper limit of normal

    5. Serum creatinine <2.0 x institutional upper limit of normal or creatinine clearance >50 mL/min (according to the Cockcroft and Gault equation).

    • Negative serum pregnancy test within 7 days prior to Cycle 1/Day 1 for women of childbearing potential.

    • All women of childbearing potential must agree to use an effective barrier method of contraception, as described in Appendix 4, during the treatment period and for at least 1 month after discontinuation of the study drug. Male subjects should use effective barrier method of contraception during the treatment period and for at least 1 month after discontinuation of the study drug

    • Ability to understand and the willingness to sign a written informed consent document.

    Exclusion Criteria:
    • Grade 3B FL or evidence of transformation to a more aggressive lymphoma

    • Prior and concomitant therapy:

    1. Prior exposure to any PI3 Kinase inhibitor

    2. Exposure to chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study or lack of recovery from adverse events (AE) due to previously administered treatments.

    3. Ongoing chronic immunosuppressants (e.g. cyclosporine) or systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drug.

    4. Other concurrent investigational agents during the study period.

    • Prior allogeneic stem cell transplant

    • Central nervous system lymphoma, including lymphomatous meningitis

    • Acute intercurrent illness including, but not limited to, active infection, unstable congestive heart failure, unstable angina pectoris, psychiatric illness or any social situation that would limit compliance with study participation requirements in the judgement of the investigator.

    • Major surgery performed within 4 weeks of study entry

    • Pregnant or nursing women

    • Active concurrent malignancy (except non-invasive non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3-years at the time of study entry.

    • Documented Human Immunodeficiency Virus (HIV)-infection

    • Active hepatitis A, hepatitis B, or hepatitis C infection

    • History of tuberculosis treatment within 2 years of study entry

    • Administration of a live vaccine within 6 weeks of first dose of study drug

    • Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening

    • Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)

    • Lymphoma that is not amenable for mandatory pre- and post-treatment biopsy as described in the inclusion criteria.

    • Unstable or severe uncontrolled medical condition (e.g. unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the patient associated with his or her participation in the study

    • Clinically significant cardiovascular abnormalities such as:

    1. QTc ≥ 470 msec.

    2. Angina not well-controlled by medication

    3. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 6 months of enrollment

    4. Symptomatic or documented congestive heart failure that meets New York Heart Association (NYHA) Class III to IV definitions;

    5. History of stroke within the last 6 months prior to screening

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbia University Medical Center New York New York United States 10019

    Sponsors and Collaborators

    • Columbia University
    • TG Therapeutics, Inc.

    Investigators

    • Principal Investigator: Changchun Deng, MD, Assistant Professor of Medicine

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Columbia University
    ClinicalTrials.gov Identifier:
    NCT03178201
    Other Study ID Numbers:
    • AAAR1223
    First Posted:
    Jun 6, 2017
    Last Update Posted:
    Jul 16, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Columbia University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Period Title: Overall Study
    STARTED 5
    COMPLETED 0
    NOT COMPLETED 5

    Baseline Characteristics

    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Overall Participants 5
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    1
    20%
    >=65 years
    4
    80%
    Sex: Female, Male (Count of Participants)
    Female
    5
    100%
    Male
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    60%
    Not Hispanic or Latino
    2
    40%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    20%
    White
    4
    80%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate
    Description The sum of patients with partial responses and complete responses.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0
    2. Secondary Outcome
    Title Progression Free Survival (PFS) After Treatment With TGR-1202
    Description The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0
    3. Secondary Outcome
    Title Duration of Response (DoR) After Treatment With TGR-1202
    Description The time of initial response until documented tumor progression.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0
    4. Secondary Outcome
    Title Number of Dose Delays
    Description The number of instances of patients having a dose of study drug delayed 1 or more days.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0
    5. Secondary Outcome
    Title Number of Dose Reductions
    Description The number of instances of patients having to reduce the dosage of study drug based on specified toxicities.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0
    6. Secondary Outcome
    Title Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
    Description Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] broken down by adverse event and CTCAE v4.0 grade of each event.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    Measure Participants 0

    Adverse Events

    Time Frame Up to 1 year post treatment
    Adverse Event Reporting Description
    Arm/Group Title TGR-1202
    Arm/Group Description Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202. TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.
    All Cause Mortality
    TGR-1202
    Affected / at Risk (%) # Events
    Total 0/5 (0%)
    Serious Adverse Events
    TGR-1202
    Affected / at Risk (%) # Events
    Total 0/5 (0%)
    Other (Not Including Serious) Adverse Events
    TGR-1202
    Affected / at Risk (%) # Events
    Total 0/5 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Ana Ignat
    Organization Columbia University
    Phone 212-305-3612
    Email ai2111@cumc.columbia.edu
    Responsible Party:
    Columbia University
    ClinicalTrials.gov Identifier:
    NCT03178201
    Other Study ID Numbers:
    • AAAR1223
    First Posted:
    Jun 6, 2017
    Last Update Posted:
    Jul 16, 2021
    Last Verified:
    Jun 1, 2021