Non-Hodgkin lymphoma MedDRA version: 20.0 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10012822 Term: Diffuse large B-c
Conditions
Sponsors
TG Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of: B-cell NHL with histological subtype limited to the following based on criteria established by the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissues: a. Follicular Lymphoma (FL) of Grade 1, 2, or 3a; b. Small Lymphocytic Lymphoma (SLL); c. Marginal Zone Lymphoma (MZL) (splenic, nodal, or extranodal); or d. Diffuse Large B-Cell Lymphoma 2. Treatment status: a. FL/SLL patients: prior treatment with one or more lines of standard therapy b. MZL patients: prior treatment with one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after the most recent systemic treatment regimen; c. DLBCL patients: relapsed or refractory to any prior standard therapy AND who are non-candidates for high-dose therapy or autologous stem cell transplant. 3. Measurable disease, defined as at least 1 measurable disease lesion >1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression. 4. 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) 5. ECOG performance status = 2 6. Male or female = 18 years of age 7. Ability to swallow and retain oral medication 8. Female patients who are not of child-bearing potential (see Appendix B- Contraceptive Guidelines and Pregnancy), and female patients of child-bearing potential who have a negative serum pregnancy test within 3 days prior to Cycle 1, Day 1. Female patients 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 either study drug, and 6 months after the last dose of bendamustine, if applicable. 9. 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 225 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 220
Exclusion criteria
Exclusion criteria: 1. Patients 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 Day 1 of Cycle 1. a. Corticosteroid therapy started at least 7 days prior to study entry (prednisone =10 mg daily or equivalent) is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted. 2. Patients who have received autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded. 3. Evidence of chronic active Hepatitis B (HBV, not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody) or chronic active Hepatitis C infection (HCV), cytomegalovirus (CMV), or known history of HIV. If HBc antibody, HCV antibody or CMV is positive the subject must be evaluated for the presence of HBV, HCV, or CMV by DNA (PCR) - See Appendix D. 4. Known history of Central Nervous System (CNS) lymphoma; patients with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture. 5. Known histological transformation from chronic lymphocytic leukemia to large cell lymphoma (i.e. Richter’s transformation) 6. Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails. 7. Live virus vaccines within 4 weeks prior to enrollment, during therapy, or for 6 weeks post-treatment. 8. History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration. 9. Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), or any drug that specifically inhibits phosphoinositide-3-kinase (PI3K) 10. 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 C – NYHA Classifications]) b. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of randomization c. Concomitant use of medication known to cause QT prolongation or torsades de pointes. d. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 6 months of enrollment 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Follicular, Small Lymphocytic and Diffuse Large B-Cell Lymphoma Cohorts: To assess the efficacy of (1) TGR-1202 alone, (2) TGR-1202 plus ublituximab, and (3) TGR-1202 plus ublituximab plus bendamustine as measured by Overall Response Rate (ORR) Marginal Zone Lymphoma Cohort: To assess the efficacy of TGR-1202 alone as measured by Overall Response Rate (ORR);Secondary Objective: Key Secondary Objectives Diffuse Large B-Cell Lymphoma Cohort: To assess the efficacy of TGR-1202 alone and in combination with ublituximab +/- bendamustine in patients with previously treated DLBCL as measured by Progression-Free Survival (PFS) at Month 6 Follicular and Small Lymphocytic Lymphoma Cohort: To assess the efficacy of TGR-1202 alone and in combination with ublituximab +/- bendamustine as measured by Complete Response (CR) rate To assess safety, tolerability and other efficacy outcomes. To analyze population pharmacokinetics and any other potential drug-drug interactions of ublituximab and TGR-1202 Exploratory objective To observe the impact of cell of origin, mutational status, and select other biomarkers on efficacy of the TGR-1202 and the ublituximab + TGR-1202 combination in patients with DLBCL;Primary end point(s): Efficacy Endpoints Overall response rate (ORR) : ORR is defined as sum of CR and PR rates.;Timepoint(s) of evaluation of this end point: During the study period, all patients will be evaluated for response by CT, PET-CT and/or MRI during cycles 3 and 6, and every 3 cycles thereafter. All baseline assessments to characterize disease will be performed within 30 days of Cycle 1 Day 1, prior to initiation of therapy. During the treatment period, all efficacy assessments have a +/- 14 day window. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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 (Cheson et al., 2007) Complete Response (CR) Rate CR rate is defined as the proportion of patients who achieve a CR Overall survival (OS) OS is defined as the interval from randomization to death from any cause Duration of Response (DOR) Duration of response is defined as the time from documentation of a response to treatment to the first documentation of tumor progression or death due to any cause whichever comes first Safety All Adverse Events (AE’s) will be reported and evaluated using National Cancer Institute’s Common Terminology Criteria (CTCAE) v4.0.;Timepoint(s) of evaluation of this end point: During the study period, all patients will be evaluated for response by CT, PET-CT and/or MRI during cycles 3 and 6, and every 3 cycles thereafter. All baseline assessments to characterize disease will be performed within 30 days of Cycle 1 Day 1, prior to initiation of therapy. During the treatment period, all efficacy assessments have a +/- 14 day window | — |
Countries
Italy, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactPallav Shah
Cambridge Regulatory Services
Outcome results
None listed