DLBCL iNHL
Conditions
Interventions
Treatment with the investigational products (IPs) CC-122 for oral
administration and IV-infusions of Onituzumab.
In the dose escalation part (Part A), CC-122 will be administered orally once
daily
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. >= 18 years of age or older at the time of signing the informed consent document., Entry Criteria Specific for Dose-Escalation Phase (Part A) 2. Subjects with CD20 positive, histologically or cytologically-confirmed, DLBCL (including transformed low grade lymphoma) who have relapsed or refractory disease following at least two prior standard treatment regimens (eg, R-CHOP or similar first-line regimen and at least one second-line salvage regimen) and/or ASCT in chemotherapy sensitive patients (see Protocol Section 7.2 for exceptions). , 3. Subjects with CD20 positive, histologically confirmed (by WHO 2008 classification [Jaffe, 2009]), FL (Grade 1, 2, or 3a) or MZL who have relapsed or refractory disease following at least one prior standard systemic treatment regimen including systemic chemo-, immune-, or chemoimmunotherapy., Entry Criteria Specific for Dose-Expansion Phase (Part B): 4.Subjects with CD20 positive, histologically confirmed FL (Grade 1, 2, or 3a) who have relapsed or refractory disease following at least one prior standard systemic treatment regimen including systemic chemo-, immune-, or chemoimmunotherapy., Lenalidomide naïve a. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-, or chemoimmunotherapy with no prior exposure to lenalidomide (FL-1 cohort). In addition, subjects must have received one prior line of salvage therapy, unless ineligible for autologous transplant. Lenalidomide exposed b. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination, and experienced outcomes to the lenalidomide treatment as follows: - Early relapse after lenalidomide treatment -Early progression after lenalidomide treatment -Disease refractory to lenalidomide - Lenalidomide or lenalidomide - containing regimen does not need to be the immediate prior regimen received by the subject to be eligible for entry., Entry Criteria that apply to both Part A and Part B 5. Bi-dimensionally measurable disease with at least one lesion > 1.5 cm in the transverse diameter. - Measurable disease cannot be previously irradiated. , 6. ECOG PS of 0 to 1. , 7. Subjects must have the following laboratory values at screening: • Absolute Neutrophil Count (ANC) >= 1.5 x 10*9/L without growth factor support for 7 days (14 days if subject received pegfilgrastim). • Hemoglobin (Hgb) >= 8 g/dL. • Platelets (plt) >= 50 x 10*9/L without transfusion for 7 days. • Potassium within normal limits or corrected with supplements. • AST/SGOT and ALT/SGPT = 60 mL/min using the Cockcroft-Gault equation.
Exclusion criteria
Exclusion criteria: 1. Prior ASCT = 1 year prior to starting study drugs. 10. Prior immunization with live virus vaccines (within 3 months prior to starting study drug) or anticipated immunization with live virus vaccines during the duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability will be assessed from AEs, laboratory tests, vital signs, ECGs, Eastern Cooperative Oncology Group Performance Status (ECOG PS), physical examinations, ophthalmologic exams, assessment of concomitant medications, and LVEF assessments. Adverse events will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) as a guide for the grading of severity. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint(s) • Preliminary efficacy of CC-122 when administered in combination with obinutuzumab as measured by tumor response, response duration, and progression-free survival (PFS). • Plasma PK parameters such as maximum observed concentration (Cmax), area under the concentration-time curve (AUC), time to maximum concentration (Tmax), terminal half-life (t1/2), apparent total body clearance (CL/F) and apparent volume of distribution (Vz/F) for CC-122 after multiple dose administration. Exploratory Endpoint(s) • Target-mediated PK disposition of obinutuzumab as assessed by non-mixed effect modeling (NONMEM) compartment analysis. • Blood PD markers of CC-122 including modulation of Aiolos in B and T cells by flow immunophenotyping, and other technologies to explore other biomarkers of interest. • Baseline and on-treatment tumor biomarkers including genetic abnormalities by exome sequencing or other technologies, RNA expression profiling, protein expression (eg, CRBN, Aiolos, Ikaros, cluster of CD10, BCL-6, MUM1, BCL-2, MYC, CD68, markers of ADCC, NK cells, and other biomarkers of interest) by immunohistochemistry or other technologies. • Relationship between the plasma concentrations of CC-122 and PD biomarkers, safety, and clinical endpoints. • Relationship between PD biomarkers and clinical endpoints, including tumor response, response duration, disease control rate and PFS. • Relationship between genetic abnormalities and clinical endpoints including tumor response, response duration, and PFS. | — |
Countries
Netherlands
Outcome results
None listed