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)
- 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
- Willingness and ability to comply with trial and follow-up procedures, and give
written informed consent
- 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
- Women who are pregnant or lactating.
- Participants requiring immediate cytoreductive therapy.