TGR-1202 (Umbralisib) in Treatment Naïve Patients With Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Umbralisib
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CLL

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)
    

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.