Clinical Trials /

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

NCT04163718

Description:

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)

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TGR-1202 (Umbralisib) in Treatment Naïve Patients With Chronic Lymphocytic Leukemia (CLL)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: MCC-19585
  • SECONDARY ID: TGR-1202-203
  • NCT ID: NCT04163718

Conditions

  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
UmbralisibTGR-1202Treatment with Umbralisib

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
Treatment with UmbralisibExperimental
  • Umbralisib

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 adequately treated basal, squamous cell carcinoma or non-melanomatous skin
             cancer, 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 and Prostate Specific Antigen (PSA) < 1.0 mg/dL on 2 consecutive
             measurements at least 3 months apart with the most recent one being within 4 weeks of
             study entry.

          -  Women who are pregnant or lactating.

          -  Participants requiring immediate cytoreductive therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (Complete Response and Partial Response)
Time Frame:Up to 24 months
Safety Issue:
Description: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

Measure:Progression Free Survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Number of Participants with Serious Adverse Events
Time Frame:Up to 24 months
Safety Issue:
Description:Number of participants with adverse events after receiving one dose of Umbralisib..

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • CLL

Last Updated

November 12, 2019