Clinical Trials Search
Clinical Trial 17682
Interventions:CC-122; CC-223; CC-292; Rituxan (rituximab); rituximab
Study Type: Treatment
Phase of Study: Phase I
- Julio Chavez
A Phase 1B, Multi-Center, Open-Label Study of Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
The primary purpose of this study is to evaluate the safety and tolerability of combinations of three new compounds (CC-122, CC-223, and CC-292) being developed to treat DLBCL and to identify the highest doses tolerated by participants to help guide the selection of doses to be studied as the compounds are further developed. Certain dose levels will also include the drug rituximab, which is currently part of the standard therapy for DLCBL. The secondary purpose is to look for early signals that the treatment is working (for example, tumor shrinkage) and compare drug levels in the body when CC-223 and CC-292 are given together.
The primary objectives of the study are to: - Determine the safety and tolerability of CC-122, CC-223 and CC-292 when administered orally as doublets, and as triplets in combination with rituximab. - Define the non-tolerated dose (NTD), the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of each combination. The secondary objectives of the study are to: - Provide information on the preliminary efficacy of each drug combination. - Characterize the steady-state pharmacokinetics (PK) of CC-223 and CC-292 following combination oral administration. The exploratory objectives of the study are to: - Characterize the steady-state pharmacokinetics of the M1 metabolite of CC-223 after oral administration of CC-223 in combination with CC-292. - Evaluate blood pharmacodynamic (PD) markers of CC-122 including modulation of cereblon (CRBN) and its substrates in B and T cells. - Evaluate blood PD markers of CC-223 including mammalian target of rapamycin (mTOR) signaling pathway biomarkers (p4E-BP1 and pAKT). - Evaluate blood PD markers of CC-292 including B-cell receptor signaling pathway biomarkers (pBTK and pERK). - Evaluate baseline tumor biomarkers including genetic abnormalities (eg, Myc, Bcl-2, mTOR pathway and other relevant genes), RNA expression profiling (GCB vs non-GCB and other genes of interest), protein expression (eg, CRBN, substrates of CRBN, CD10, BCL-6, MUM1, BCL-2, MYC) and other biomarkers of interest ( eg epigenetic markers). - Explore the effect of study treatments on tumor biomarkers, including CRBN and substrates of CRBN, B-cell receptor and mTOR signaling pathways, RNA expression, apoptosis, and cellular proliferation. - Explore the relationship between systemic exposure of CC-122, CC-223, CC-292 and relevant metabolites and PD biomarkers. - Explore the relationship between PD biomarkers and clinical activity. - Explore [18F]- whole body fluorodeoxyglucose-positron emission tomography (FDG)- PET imaging as a measure of PD and clinical activity.