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)

• Sponsor: Celgene (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03930953
• Collaborator: (none)
• Enrollment: 210
• Locations: 48
• Arms: 2
• Anticipated Duration (Months): 79.1
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Drug: CC-99282; Drug: Rituximab; Drug: Obinutuzumab; Drug: Tafasitamab; Drug: Tazemetostat	Phase 1

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 administered at or below MTD in subjects with R/R DLBCL and NHL. Part B will also evaluate the safety and preliminary efficacy of CC-99282 in combination with anti-lymphoma agents in participants with R/R DLBCL and R/R FL.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 210 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, 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).
• Actual Study Start Date: May 20, 2019
• Anticipated Primary Completion Date: Dec 20, 2024
• Anticipated Study Completion Date: Dec 21, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Dose Escalation	Drug: CC-99282; Specified dose on specified days
Experimental: Part B: Dose Expansion	Drug: CC-99282; Specified dose on specified days; Drug: Rituximab; Specified dose on specified days; Drug: Obinutuzumab; Specified dose on specified days; Drug: Tafasitamab; Specified dose on specified days; Drug: Tazemetostat; Specified dose on specified days

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicity (DLT) [Up to 28 days in Cycle 1]

2. Maximum tolerated dose (MTD) [Up to 28 days in cycle 1]

3. Incidence of Adverse Events (AEs) [From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 2 years)]

Secondary Outcome Measures

1. Pharmacokinetics - Maximum observed plasma concentration (Cmax) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

2. Pharmacokinetics - Area under the plasma concentration-time curve (AUC) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

3. Pharmacokinetics - Time to Cmax (Tmax) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

4. Pharmacokinetics - Terminal-phase elimination half-life (t1/2) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

5. Pharmacokinetics - Apparent total clearance of the drug from plasma after oral administration (CL/F) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

6. Pharmacokinetics: Apparent volume of distribution during terminal phase after non-intravenous administration (V/F) [Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)]

7. Objective response rate (ORR) [Up to approximately 3 years]

8. Time to response (TTR) [Up to approximately 3 years]

9. Duration of response (DoR) [Up to approximately 3 years]

10. Progression free survival: Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause [Up to approximately 3 years]

11. Overall survival: Time from first dose of CC-99282 to death from any cause [Up to approximately 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Irvine	Orange	California	United States	92848
2	University of California, Irvine	Orange	California	United States	92848
3	H Lee Moffitt Cancer Center	Tampa	Florida	United States	32207
4	University Of Kansas Cancer Center	Overland Park	Kansas	United States	66210
5	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota	United States	55905
6	Washington University	Saint Louis	Missouri	United States	63110
7	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
8	Perlmutter Cancer Center at NYU Langone Hospital-Long Island	Mineola	New York	United States	11501
9	MD Anderson Cancer Center	Houston	Texas	United States	77030
10	LKH - Universitätsklinikum der PMU Salzburg	Salzburg		Austria	5020
11	Universitätsklinikum St. Pölten	Sankt Pölten		Austria	3100
12	Medical University Vienna	Vienna		Austria	1090
13	UZ Antwerpen	Edegem		Belgium	2650
14	UZ Leuven	Leuven		Belgium	3000
15	Cross Cancer Institute University of Alberta	Edmonton	Alberta	Canada	T6G1Z2
16	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
17	McGill University Health Centre MUHC	Montreal		Canada	H3H 2R9
18	Aarhus University Hospital	Aarhus C		Denmark	DK-8000
19	Rigshospitalet University Hospital	Copenhagen		Denmark	2100
20	Vejle Hospital	Vejle		Denmark	7100
21	Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux		France	33076
22	Hopital Henri Mondor	Creteil		France	94010
23	Local Institution - 403	Creteil		France	94010
24	CHRU de Lille - Hopital Claude Huriez	Lillie Cedex		France	59037
25	Local Institution - 406	Lillie Cedex		France	59037
26	Local Institution - 0904	Montpellier CEDEX 5		France	34295
27	Centre Hospitalier Lyon-Sud	Pierre-Benite CEDEX		France	69495
28	Centre Henri Becquerel	Rouen		France	76038
29	Institut Claudius Regaud, IUCT-Oncopole	Toulouse		France	31059
30	Gustave Roussy	Villejuif CEDEX		France	94805
31	Local Institution - 401	Villejuif CEDEX		France	94805
32	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo		Italy	24127
33	Local Institution - 504	Bologna		Italy	40138
34	ASST Grande Ospedale Metropolitano Niguarda, Milano	Milano		Italy	20162
35	Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"	Napoli		Italy	80131
36	Hospital Universitari Germans Trias i Pujol Can Ruti	Badalona (Barcelona)		Spain	08916
37	Local Institution - 301	Barcelona		Spain	08035
38	Vall d´Hebron University Hospital	Barcelona		Spain	08035
39	Fundacion Jimenez Daaz	Madrid		Spain	28040
40	Hospital La Paz	Madrid		Spain	28046
41	Local Institution - 304	Madrid		Spain	28046
42	Hospital Universitario Virgen De La Victoria	Malaga		Spain	29010
43	Local Institution - 303	Malaga		Spain	29010
44	Hospital Universitario de Salamanca	Salamanca		Spain	37007
45	Local Institution - 0905	Belfast Northern Ireland		United Kingdom	BT9 7AB
46	Western General Hospital	Edinburgh Scotland		United Kingdom	EH4 2XU
47	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2BU
48	Southampton General Hospital	Southhampton		United Kingdom	SO01 6YD

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls
• Investigator Inquiry Form

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT03930953
• Other Study ID Numbers: CC-99282-NHL-001; U1111-1224-5399; 2018-003235-29
• First Posted: Apr 29, 2019
• Last Update Posted: Aug 2, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celgene: Non-Hodgkin Lymphomas (NHL); Safety; Efficacy; CC-99282; Rituximab; Relapsed; Refractory; Pharmacokinetics; Obinutuzumab; Tafasitamab; Tazemetostat; Anti-lymphoma agents
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Obinutuzumab

Study Results

No Results Posted as of Aug 2, 2022