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
- 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 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) 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 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 Pharmacokinetics - 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
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) criteriaDOR Up to approximately 4 years Determined using the modified International PCNSL Collaborative Group (IPCG) criteria
Trial Locations
- Locations (90)
Local Institution - 114
🇺🇸Los Angeles, California, United States
Rigshospitalet University Hospital
🇩🇰Copenhagen, Denmark
Local Institution - 603
🇩🇰Vejle, Denmark
Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
🇫🇷Bordeaux, France
Hopital Henri Mondor
🇫🇷Creteil, France
Chru De Lille - Hopital Claude Huriez
🇫🇷Lillie Cedex, France
Local Institution - 0904
🇫🇷Montpellier CEDEX 5, France
CHU Montpellier - Hopital St Eloi
🇫🇷Montpellier, France
Hopital Saint-Louis
🇫🇷Paris, France
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Benite CEDEX, France
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Local Institution - 658
🇨🇳Guangzhou, China
Mayo Clinic Arizona - Scottsdale
🇺🇸Scottsdale, Arizona, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
H Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
The University of Kansas - Clinical Research Center
🇺🇸Overland Park, Kansas, United States
University Of Maryland At Baltimore
🇺🇸Baltimore, Maryland, United States
Mayo Clinic in Rochester, Minnesota
🇺🇸Rochester, Minnesota, United States
Local Institution - 104
🇺🇸Saint Louis, Missouri, United States
Local Institution - 103
🇺🇸Hackensack, New Jersey, United States
Local Institution - 106
🇺🇸Mineola, New York, United States
Perlmutter Cancer Center at NYU Langone Hospital-Long Island
🇺🇸Mineola, New York, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital Aleman
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 251
🇦🇷Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 254
🇦🇷Pilar, Buenos Aires, Argentina
Local Institution - 250
🇦🇷Buenos Aires, Argentina
Local Institution - 253
🇦🇷Buenos Aires, Argentina
Local Institution - 252
🇦🇷Cordoba, Argentina
Local Institution - 701
🇦🇹Salzburg, Austria
Local Institution - 704
🇦🇹St. Polten, Austria
Local Institution - 703
🇦🇹Vienna, Austria
Local Institution - 903
🇧🇪Edegem, Belgium
Local Institution - 901
🇧🇪Leuven, Belgium
Local Institution - 902
🇧🇪Leuven, Belgium
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital israelita Albert Einstein
🇧🇷Sao Paulo, Sp, Brazil
Instituto D'Or de Pesquisa e Ensino (IDOR)
🇧🇷São Paulo, Brazil
Local Institution - 452
🇧🇷São Paulo, Brazil
Local Institution - 203
🇨🇦Edmonton, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Clínica Inmunocel
🇨🇱Santiago, Metropolitana DE Santiago, Chile
Bradford Hill
🇨🇱Recoleta, Metropolitana, Chile
Fundacion Oncologia Arturo Lopez Perez
🇨🇱Santiago, Metropolitana, Chile
Pontificia Universidad Catolica de Chile-Hemato-Oncology
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 350
🇨🇱Santiago, RM, Chile
Local Institution - 0909
🇨🇱Santiago, Chile
Local Institution - 351
🇨🇱Santiago, Chile
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Local Institution - 656
🇨🇳Xiamen, Fujian, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Local Institution - 652
🇨🇳Haerbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan Shi, Hubei, China
The First Affiliated Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Local Institution - 654
🇨🇳Hangzhou, Zhejiang, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, China
Centre Henri Becquerel
🇫🇷Rouen, France
Institut Claudius Regaud, IUCT-Oncopole
🇫🇷Toulouse, France
Gustave Roussy
🇫🇷Villejuif CEDEX, France
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Local Institution - 151
🇮🇱Petah Tikva, Israel
The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric Hemato-Oncology
🇮🇱Ramat Gan, Israel
Azienda Ospedaliera Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Azienda Ospedaliero Universitaria di Bologna
🇮🇹Bologna, Italy
Local Institution - 503
🇮🇹Milano, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale
🇮🇹Napoli, Italy
Local Institution - 506
🇮🇹Pavia, Italy
Local Institution - 505
🇮🇹Rozzano, Italy
Local Institution - 507
🇮🇹Verona, Italy
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Local Institution - 306
🇪🇸Badalona (Barcelona), Spain
Vall d Hebron University Hospital
🇪🇸Barcelona, Spain
Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology
🇪🇸Madrid, Spain
Hospital La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen De La Victoria
🇪🇸Malaga, Spain
Local Institution - 305
🇪🇸Salamanca, Spain
Local Institution - 0905
🇬🇧Belfast Northern Ireland, United Kingdom
Local Institution - 805
🇬🇧Belfast Northern Ireland, United Kingdom
Western General Hospital
🇬🇧Edinburgh Scotland, United Kingdom
Southampton General Hospital
🇬🇧Southhampton, United Kingdom