A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Registration Number
- NCT03930953
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-99282 alone and in combination with anti-lymphoma agents in participants with relapsed or refractory non-Hodgkin's lymphomas.
- Detailed Description
Participants with relapsed or refractory non-Hodgkin's lymphomas (R/R NHL) who have failed at least 2 lines of therapy (or have received at least one prior line of standard therapy and are not eligible for any other therapy).
The dose escalation will evaluate the safety and tolerability of escalating doses of CC-99282 in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and/or relapsed or refractory follicular lymphoma (R/R FL) participants to determine the maximum tolerated dose (MTD) of CC-99282 as monotherapy.
The dose expansion will further evaluate the safety and preliminary efficacy of single agent CC-99282 or the safety and preliminary efficacy of CC-99282 in combination with anti-lymphoma agents in participants with R/R DLBCL and NHL.
Part B Cohort B will further evaluate the potential effects of food on the PK and safety of CC-99282.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 438
- History of Non-Hodgkin's Lymphoma (NHL) with relapsed or refractory disease
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Life expectancy ≤ 2 months
- Received prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting CC-99282, whichever is shorter
- Is on chronic systemic immunosuppressive therapy or corticosteroids or has clinically significant graft-versus-host disease (GVHD)
- Impaired cardiac function or clinically significant cardiac disease
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Dose Escalation CC-99282 - Part B: Dose Expansion CC-99282 - Part B: Dose Expansion Rituximab - Part B: Dose Expansion Obinutuzumab - Part B: Dose Expansion Tafasitamab - Part B: Dose Expansion Valemetostat -
- Primary Outcome Measures
Name Time Method Incidence of Adverse Events (AEs) From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Number of participants with vital sign abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Number of participants with laboratory abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Maximum tolerated dose (MTD) Up to 28 days in cycle 1 Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Number of participants with electrocardiogram (ECG) abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years) Dose Limiting Toxicity (DLT) Up to 28 days in Cycle 1 Number of participants with physical examination abnormalities From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Up to approximately 6 years Time from first dose of CC-99282 to death from any cause
Determined by the Lugano Classification for NHL response criteriaORR Up to approximately 4 years Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).
Determined using the modified International PCNSL Collaborative Group (IPCG) criteriaPharmacokinetics - Terminal-phase elimination half-life (T-HALF) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Pharmacokinetics - Apparent total body clearance of the drug from the plasma (CLT/F) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Pharmacokinetics: Apparent volume of distribution (Vz/F) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Pharmacokinetics - Maximum plasma concentration of drug (Cmax) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Pharmacokinetics - Area under the plasma concentration-time curve (AUC) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax) Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) Objective response rate (ORR) Up to approximately 6 years Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).
Determined by the Lugano Classification for NHL response criteriaTime to response (TTR) Up to approximately 6 years Determined by the Lugano Classification for NHL response criteria
Duration of response (DoR) Up to approximately 6 years Determined by the Lugano Classification for NHL response criteria
Progression free survival (PFS) Up to approximately 6 years Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
Determined by the Lugano Classification for NHL response criteriaTTR Up to approximately 4 years Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
PFS Up to approximately 4 years Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
OS Up to approximately 4 years Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
DOR Up to approximately 4 years Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
Trial Locations
- Locations (66)
Local Institution - 109
🇺🇸Scottsdale, Arizona, United States
Local Institution - 111
🇺🇸Jacksonville, Florida, United States
Local Institution - 102
🇺🇸Tampa, Florida, United States
Local Institution - 108
🇺🇸Overland Park, Kansas, United States
Local Institution - 107
🇺🇸Rochester, Minnesota, United States
Local Institution - 104
🇺🇸Saint Louis, Missouri, United States
Local Institution - 103
🇺🇸Hackensack, New Jersey, United States
Local Institution - 101
🇺🇸Houston, Texas, United States
Local Institution - 255
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 254
🇦🇷Pilar, Buenos Aires, Argentina
Scroll for more (56 remaining)Local Institution - 109🇺🇸Scottsdale, Arizona, United States