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)

Lymphoma, Non-Hodgkin Clinical Trial

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03930953
• Other study ID #: CC-99282-NHL-001
• Secondary ID: U1111-1224-53992
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 20, 2019
• Est. completion date: April 18, 2027

Study information

• Verified date: May 2024
• Source: Celgene
• Contact: BMS Study Connect Contact Center http://www.bmsstudyconnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 438
• Est. completion date: April 18, 2027
• Est. primary completion date: April 17, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• CC-99282
Specified dose on specified days
• Rituximab
Specified dose on specified days
• Obinutuzumab
Specified dose on specified days
• Tafasitamab
Specified dose on specified days
• Valemetostat
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 250	Buenos Aires
Argentina	Local Institution - 253	Buenos Aires
Argentina	Hospital Aleman	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 251	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 252	Cordoba
Argentina	Local Institution - 254	Pilar	Buenos Aires
Austria	Local Institution - 701	Salzburg
Austria	Local Institution - 704	St. Polten
Austria	Local Institution - 703	Vienna
Belgium	Local Institution - 903	Edegem
Belgium	Local Institution - 901	Leuven
Belgium	Local Institution - 902	Leuven
Brazil	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	São Paulo
Brazil	Local Institution - 452	São Paulo
Canada	Local Institution - 203	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Chile	Bradford Hill	Recoleta	Metropolitana
Chile	Centro de Oncologia de Precision	Santiago	RM
Chile	Clínica Inmunocel	Santiago	Metropolitana DE Santiago
Chile	Fundacion Oncologia Arturo Lopez Perez	Santiago	Metropolitana
Chile	Local Institution - 0909	Santiago
Chile	Local Institution - 351	Santiago
Chile	Local Institution - 352	Santiago	Metropolitana
China	Peking University Third Hospital	Beijing	Beijing
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Local Institution - 658	Guangzhou
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Local Institution - 652	Haerbin	Heilongjiang
China	Local Institution - 654	Hangzhou	Zhejiang
China	Local Institution - 650	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospital	Wuhan Shi	Hubei
China	Local Institution - 656	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan
Denmark	Aarhus University Hospital	Aarhus
Denmark	Local Institution - 601	Copenhagen
Denmark	Local Institution - 603	Vejle
France	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	CHU Montpellier - Hopital St Eloi	Montpellier
France	Local Institution - 0904	Montpellier CEDEX 5
France	Hopital Saint-Louis	Paris
France	Centre Hospitalier Lyon-Sud	Pierre-Benite CEDEX
France	Centre Henri Becquerel	Rouen
France	Institut Claudius Regaud, IUCT-Oncopole	Toulouse
France	Gustave Roussy	Villejuif CEDEX
Israel	Local Institution - 150	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
Italy	Azienda Ospedaliera Papa Giovanni Xxiii	Bergamo
Italy	Azienda Ospedaliero Universitaria di Bologna	Bologna
Italy	Local Institution - 503	Milano
Italy	Local Institution - 502	Napoli
Italy	Local Institution - 506	Pavia
Italy	Local Institution - 505	Rozzano
Italy	Local Institution - 507	Verona
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul
Spain	Local Institution - 306	Badalona (Barcelona)
Spain	Vall d Hebron University Hospital	Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology	Madrid
Spain	Local Institution - 304	Madrid
Spain	Hospital Universitario Virgen De La Victoria	Malaga
Spain	Local Institution - 305	Salamanca
United Kingdom	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 States	University Of Maryland At Baltimore	Baltimore	Maryland
United States	Local Institution - 103	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Local Institution - 114	Los Angeles	California
United States	Perlmutter Cancer Center at NYU Langone Hospital-Long Island	Mineola	New York
United States	University of California, Irvine	Orange	California
United States	The University of Kansas - Clinical Research Center	Overland Park	Kansas
United States	The University of Kansas - Clinical Research Center	Overland Park	Kansas
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	Mayo Clinic Arizona - Scottsdale	Scottsdale	Arizona
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Denmark,  France,  Israel,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Dose Limiting Toxicity (DLT)		Up to 28 days in Cycle 1
Primary	Maximum tolerated dose (MTD)		Up to 28 days in cycle 1
Secondary	Pharmacokinetics - Maximum plasma concentration of drug (Cmax)		Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Secondary	Pharmacokinetics - Area under the plasma concentration-time curve (AUC)		Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Secondary	Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax)		Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Secondary	Pharmacokinetics - Terminal-phase elimination half-life (T-HALF)		Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Secondary	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)
Secondary	Pharmacokinetics: Apparent volume of distribution (Vz/F)		Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Secondary	Objective response rate (ORR)	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 criteria	Up to approximately 6 years
Secondary	Time to response (TTR)	Determined by the Lugano Classification for NHL response criteria	Up to approximately 6 years
Secondary	Duration of response (DoR)	Determined by the Lugano Classification for NHL response criteria	Up to approximately 6 years
Secondary	Progression free survival (PFS)	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 criteria	Up to approximately 6 years
Secondary	Overall survival (OS)	Time from first dose of CC-99282 to death from any cause; Determined by the Lugano Classification for NHL response criteria	Up to approximately 6 years
Secondary	ORR	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) criteria	Up to approximately 4 years
Secondary	TTR	Determined using the modified International PCNSL Collaborative Group (IPCG) criteria	Up to approximately 4 years
Secondary	DOR	Determined using the modified International PCNSL Collaborative Group (IPCG) criteria	Up to approximately 4 years
Secondary	PFS	Determined using the modified International PCNSL Collaborative Group (IPCG) criteria	Up to approximately 4 years
Secondary	OS	Determined using the modified International PCNSL Collaborative Group (IPCG) criteria	Up to approximately 4 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting