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

NCT ID: NCT04163718

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-12
• Study Completion Date: 2022-10-19

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)

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment with Umbralisib

Group Type: EXPERIMENTAL

Umbralisib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

TGR-1202

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TG Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Pinilla, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Countries

United States

References

Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.

Reference Type: DERIVED

PMID: 34398557 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

TGR-1202-203

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-19585

Identifier Type: -

Identifier Source: org_study_id