Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Ublituximab
Product Code: TG-1101
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Ublituximab
CAS Number: 1174014-05-1
Current Sponsor code: TG-1101
Other descriptive na
Sponsors
TG Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: 1. B-cell CLL (treatment naïve or previously treated) that warrants treatment consistent with accepted IWCLL criteria (Hallek 2008) 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 100.5°F or 38.0°C for =2 weeks, or iv. Night sweats for >1 month. 2. Adequate organ system function, defined as follows: a. Absolute neutrophil count (ANC) > 1,000/mm3 (µL) / platelet count > 50,000/mm3 (µL). b. Total bilirubin =1.5 times the upper limit of normal (ULN). c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 x ULN if no liver involvement or =5 x the ULN if known liver involvement. d. Calculated creatinine clearance >30 mL/min (as calculated by the Cockcroft-Gault formula). 3. Presence of measurable lymphadenopathy, defined as the presence of = 1 nodal lesion that measures = 2.0 cm in the longest diameter (LD) and = 1.0 cm in the longest perpendicular diameter (LPD) as assessed by computed tomography (CT) or magnetic resonance imaging (MRI). 4. ECOG performance status = 2. 5. Male or female = 18 years of age. 6. Ability to swallow and retain oral medication. 7. Female subjects who are not of child-bearing potential (see Appendix B- Contraceptive Guidelines and Pregnancy), and female subjects of child-bearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1. Female subjects of child-bearing potential, and male partners must consent to use a medically acceptable method of contraception throughout the study period and for 4 months after the last dose of ublituximab or TGR-1202, or 18 months after the last dose of obinutuzumab or at least 4 weeks after the last dose of chlorambucil. 8. Willingness and ability to comply with trial and follow-up procedures and give written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 303
Exclusion criteria
Exclusion criteria: 1. Subjects receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization) or any investigational drug within 21 days of Cycle 1/Day 1 (contact sponsor for 470 msec d. Angina not well-controlled by medication e. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 6 months of randomization. 11. Malignancy 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 BCG within 6 months, localized prostate cancer and 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. 12. Women who are pregnant or lactating.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy;Timepoint(s) of evaluation of this end point: Efficacy will be evaluated every three months | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish that the combination of ublituximab + umbralisib is superior to the combination of obinutuzumab + chlorambucil as measured by Progression-Free Survival (PFS) in patients with CLL;Secondary Objective: To establish that the combination of ublituximab + umbralisib provides clinical benefit over both ublituximab alone and umbralisib alone. To evaluate and compare the combination of ublituximab + umbralisib to the combination of obinutuzumab + chlorambucil with respect to overall response rate in patients with CLL To assess safety, tolerability and other efficacy outcomes. To determine the pharmacokinetics and any potential drug-drug interactions of ublituximab and umbralisib in combination. ;Primary end point(s): Progression-free survival (PFS) PFS is defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression based on standard criteria (Hallek et al. 2008) and occurring for any reason (i.e., increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis. Overall response rate (ORR) ORR is defined as sum of CR, CRi, PR and nPR rates. Complete Response (CR) Rate CR rate is defined as the proportion of patients who achieve a CR or CRi. Minimal Residual Disease (MRD) Negativity Rate MRD negativity rate is defined as the proportion of patients who are MRD negative. Duration of response (DOR) DOR is defined as the interval from the first documentation of CR, CRi, PR or nPR to the earlier of the first documentation of definitive disease progression or death from any cause. Overall Survival (OS) OS is defined as the interval from randomization to death from any cause. ;Timepoint(s) of evaluation of this end point: Each primary end points will be evaluated every three months | — |
Countries
Bulgaria, Israel, Italy, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactIzabela Kozdras-Urbanek
Brillance Sp. z o.o.
Outcome results
None listed