TGR-1202 (Umbralisib) in Treatment Naïve Patients With Chronic Lymphocytic Leukemia (CLL)

Sponsor
H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Suspended
CT.gov ID
NCT04163718
Collaborator
TG Therapeutics, Inc. (Industry)
35
Enrollment
1
Location
1
Arm
47.6
Anticipated Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to see how safe and effective the investigational drug umbralisib (TGR-1202) is in individuals with Chronic Lymphocytic Leukemia (CLL)

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
35 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study to Assess the Efficacy, Safety, Pharmacokinetic and Pharmacodynamic Parameters of Umbralisib in Treatment Naïve Patients With Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Nov 12, 2019
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment with Umbralisib

Drug: Umbralisib
800 mg Umbralisib will be self-administered on an outpatient basis. Umbralisib will be taken orally once daily within 30 minutes of a meal until removal from study. This treatment will be administered in 4 week (28-day) cycles.
Other Names:
  • TGR-1202
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (Complete Response and Partial Response) [Up to 24 months]

      Overall Response Rate (ORR) of Umbralisib Treatment will be determined according to the criteria of the International Workshop on Chronic Lymphocytic Leukemia. ORR is defined as the percent of participants who achieve Complete Response (CR) or Partial Response (PR).

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [Up to 24 months]

      Progression Free Survival (PFS) is defined as the interval from registration to the earlier of the first documentation of definitive disease progression or death from any cause.

    2. Number of Participants with Serious Adverse Events [Up to 24 months]

      Number of participants with adverse events after receiving one dose of Umbralisib..

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • A diagnosis of B-cell CLL that has not been previously treated and now warrants treatment consistent with accepted iwCLL criteria (Hallek 2018) for initiation of therapy. Any one of the following conditions constitute CLL that warrants treatment: (a) Evidence of progressive marrow failure as manifested by the onset or worsening of anemia and/or thrombocytopenia, or (b) Massive (i.e., lower edge of spleen ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or (c) Massive (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or (d) Progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (ALC) >50% over a 2-month period or lymphocyte doubling time of <6 months (as long as initial ALC was ≥30,000/µL), or e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or (f) Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, or spine), or (g) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs occurring in the absence of evidence of infection: (i) Unintentional weight loss of ≥10% within the previous 6 months, or (ii) Significant fatigue (≥ Grade 2), or (iii) Fevers >100.5°F or 38.0°C for ≥2 weeks, or (iv) Night sweats for >1 month.

    • Adequate organ system function as defined per protocol.

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

    • Ability to swallow and retain oral medication

    • Female participants who are not of child-bearing potential and female participants of child-bearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1. Female participants of child-bearing potential and all male partners, and male participants must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after the last dose of study drug.

    • Willingness and ability to comply with trial and follow-up procedures, and give written informed consent

    Exclusion Criteria:
    • Has ever received any form of treatment for CLL.

    • Corticosteroid therapy of prednisone > 10 mg or equivalent started at least 7 days prior to Cycle 1, Day 1 is prohibited. Prednisone ≤ 10 mg daily or equivalent is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.

    • Prior treatment with umbralisib.

    • Prior treatment with autologous hematologic stem cell transplant or prior Allogeneic hematologic stem cell transplant is excluded.

    • Evidence of chronic active Hepatitis B (HBV, not including participants with prior hepatitis B vaccination; or positive serum Hepatitis B antibody) or chronic active Hepatitis C infection (HCV), active cytomegalovirus (CMV), or known history of HIV.

    • Known histological transformation from CLL to an aggressive lymphoma (i.e. Richter's transformation / Hodgkin Lymphoma).

    • Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infection of skin/nails. NOTE: Participants may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion. Use of anti-pneumocystis and antiviral prophylaxis is required.

    • Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis)

    • Malabsorption syndromes

    • Irritable bowel syndrome with greater than 3 loose stools per day as a baseline.

    • Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:(a) Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV) - See Appendix B (b) Myocardial infarction within 6 months of enrollment (c) Concomitant use of medication known to cause QT prolongation or torsades de pointes should be used with caution and at investigator discretion. (d) Angina not well-controlled by medication (e) Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), symptomatic peripheral arterial disease, angioplasty, cardiac/vascular stenting within 6 months of enrollment.

    • Malignancy, including myelodysplastic syndromes, within 3 years of study enrollment except for basal, squamous cell carcinoma or melanoma in situ, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer following curative treatment and with a normal PSA.

    • Women who are pregnant or lactating.

    • Participants requiring immediate cytoreductive therapy.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1H. Lee Moffitt Cancer Center & Research InstituteTampaFloridaUnited States33612

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute
    • TG Therapeutics, Inc.

    Investigators

    • Principal Investigator: Javier Pinilla, MD, PhD, Moffitt Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT04163718
    Other Study ID Numbers:
    • MCC-19585
    • TGR-1202-203
    First Posted:
    Nov 15, 2019
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by H. Lee Moffitt Cancer Center and Research Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 23, 2022