Clinical trial NCT03930953: 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)
Official title: A Phase 1/2, Multi-center, Open-label Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of an Orally Available Small Molecule, CC-99282, Alone and in Combination With Anti-Lymphoma Agents in Subjects With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkin Lymphomas (NHL)
Safety
Efficacy
CC-99282
Rituximab
Relapsed
Refractory
Pharmacokinetics
Obinutuzumab
Tafasitamab
Valemetostat
Anti-lymphoma agents
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2019-04-29
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with laboratory abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with vital sign abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with electrocardiogram (ECG) abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Number of participants with physical examination abnormalities
timeFrame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
measure: Dose Limiting Toxicity (DLT)
timeFrame: Up to 28 days in Cycle 1
measure: Maximum tolerated dose (MTD)
timeFrame: Up to 28 days in cycle 1
Secondary outcomes:
measure: Pharmacokinetics - Maximum plasma concentration of drug (Cmax)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Pharmacokinetics - Area under the plasma concentration-time curve (AUC)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Pharmacokinetics - Terminal-phase elimination half-life (T-HALF)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Pharmacokinetics - Apparent total body clearance of the drug from the plasma (CLT/F)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Pharmacokinetics: Apparent volume of distribution (Vz/F)
timeFrame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
measure: Objective response rate (ORR)
timeFrame: Up to approximately 6 years
measure: Time to response (TTR)
timeFrame: Up to approximately 6 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 6 years
measure: Progression free survival (PFS)
timeFrame: Up to approximately 6 years
measure: Overall survival (OS)
timeFrame: Up to approximately 6 years
measure: ORR
timeFrame: Up to approximately 4 years
measure: TTR
timeFrame: Up to approximately 4 years
measure: DOR
timeFrame: Up to approximately 4 years
measure: PFS
timeFrame: Up to approximately 4 years
measure: OS
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona - Scottsdale
state: Arizona
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Local Institution - 114
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Whittier
country: United States
facility: Oncology Institute of Hope and Innovation
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Overland Park
country: United States
facility: The University of Kansas - Clinical Research Center
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas - Clinical Research Center
state: Kansas
city: Baltimore
country: United States
facility: University Of Maryland At Baltimore
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Local Institution - 104
state: Missouri
city: Hackensack
country: United States
facility: Local Institution - 103
state: New Jersey
city: Mineola
country: United States
facility: Local Institution - 106
state: New York
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital-Long Island
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Aleman
state: Buenos Aires
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 251
state: Buenos Aires
city: Pilar
country: Argentina
facility: Local Institution - 254
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 250
city: Buenos Aires
country: Argentina
facility: Local Institution - 253
city: Cordoba
country: Argentina
facility: Local Institution - 252
city: Salzburg
country: Austria
facility: Local Institution - 701
city: St. Polten
country: Austria
facility: Local Institution - 704
city: Vienna
country: Austria
facility: Local Institution - 703
city: Edegem
country: Belgium
facility: Local Institution - 903
city: Leuven
country: Belgium
facility: Local Institution - 901
city: Leuven
country: Belgium
facility: Local Institution - 902
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital israelita Albert Einstein
state: Sp
city: São Paulo
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino (IDOR)
city: São Paulo
country: Brazil
facility: Local Institution - 452
city: Edmonton
country: Canada
facility: Local Institution - 203
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Santiago
country: Chile
facility: Clínica Inmunocel
state: Metropolitana DE Santiago
city: Recoleta
country: Chile
facility: Bradford Hill
state: Metropolitana
city: Santiago
country: Chile
facility: Fundacion Oncologia Arturo Lopez Perez
state: Metropolitana
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile-Hemato-Oncology
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 350
state: RM
city: Santiago
country: Chile
facility: Local Institution - 0909
city: Santiago
country: Chile
facility: Local Institution - 351
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Xiamen
country: China
facility: Local Institution - 656
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Haerbin
country: China
facility: Local Institution - 652
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan Shi
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 654
state: Zhejiang
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Guangzhou
country: China
facility: Local Institution - 658
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet University Hospital
city: Vejle
country: Denmark
facility: Local Institution - 603
city: Bordeaux
country: France
facility: Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lillie Cedex
country: France
facility: Chru De Lille - Hopital Claude Huriez
city: Montpellier CEDEX 5
country: France
facility: Local Institution - 0904
city: Montpellier
country: France
facility: CHU Montpellier - Hopital St Eloi
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pierre-Benite CEDEX
country: France
facility: Centre Hospitalier Lyon-Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Claudius Regaud, IUCT-Oncopole
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Local Institution - 151
city: Ramat Gan
country: Israel
facility: The Edmond and Lily Safra Children's Hospital The Chaim Sheba Medical Center Department of Pediatric Hemato-Oncology
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna
city: Milano
country: Italy
facility: Local Institution - 503
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale
city: Pavia
country: Italy
facility: Local Institution - 506
city: Rozzano
country: Italy
facility: Local Institution - 505
city: Verona
country: Italy
facility: Local Institution - 507
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital
city: Badalona (Barcelona)
country: Spain
facility: Local Institution - 306
city: Barcelona
country: Spain
facility: Vall d Hebron University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology
city: Madrid
country: Spain
facility: Hospital La Paz
city: Malaga
country: Spain
facility: Hospital Universitario Virgen De La Victoria
city: Salamanca
country: Spain
facility: Local Institution - 305
city: Belfast Northern Ireland
country: United Kingdom
facility: Local Institution - 0905
city: Belfast Northern Ireland
country: United Kingdom
facility: Local Institution - 805
city: Edinburgh Scotland
country: United Kingdom
facility: Western General Hospital
city: Southhampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: