A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Rituximab in Subjects With Relapsed or Refractory Non-hodgkin Lymphomas (R/R NHL)

• ClinicalTrials.gov Identifier: NCT03930953
• Recruitment Status: Recruiting
• First Posted: April 29, 2019
• Last Update Posted: January 14, 2021
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Study Description

Brief Summary:

CC-99282-NHL-001 study is a Phase I dose escalation and expansion clinical study of CC-99282 administered alone and in combination with rituximab in subjects with relapsed or refractory non-hodgkin Lymphomas (R/R NHL).

Condition or disease	Intervention/treatment	Phase
Lymphoma, Non-Hodgkin	Drug: CC-99282; Drug: rituximab	Phase 1

Detailed Description:

Subjects with 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 R/R DLBCL and/or R/R FL subjects to determine the 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 rituximab in subjects with R/R DLBCL and R/R FL.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, 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 Rituximab in Subjects With Relapsed or Refractory Non-Hodgkin Lymphoma (R/R iNHL).
• Actual Study Start Date: May 20, 2019
• Estimated Primary Completion Date: June 11, 2023
• Estimated Study Completion Date: May 13, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Administration of CC-99282; Escalating doses of CC-99282 administered orally once daily on intermittent schedules up to 2 years.	Drug: CC-99282; CC-99282
Experimental: CC-99282 + rituximab; CC-99282 administered orally once daily on intermittent schedule with rituximab intravenously (IV) 375 mg/m2 weekly in Cycle 1, every 28 days in C2-6, then every 8 weeks through 2 years.	Drug: CC-99282; CC-99282; Drug: rituximab; rituximab

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity (DLT) [ Time Frame: up to 28 days in Cycle 1 ]
   Number of subjects with a DLT
2. Maximum tolerated dose (MTD) [ Time Frame: up to 28 days in cycle 1 ]
   The highest dose of CC-99282 associated with acceptable safety and tolerability
3. Adverse Events (AEs) [ Time Frame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 2 years) ]
   Type, frequency, seriousness, severity and relationship of AEs to CC-99282 and rituximab; changes from baseline in clinically-relevant physical findings, vital signs, selected analytes, ECGs, LVEF and ECOG

Secondary Outcome Measures :

1. Pharmacokinetics - Cmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Maximum observed plasma concentration
2. Pharmacokinetics - AUC [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Area under the plasma concentration-time curve
3. Pharmacokinetics - Tmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Time to Cmax
4. Pharmacokinetics - t1/2 [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Terminal-phase elimination half-life
5. Pharmacokinetics - CL/F [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Apparent total clearance of the drug from plasma after oral administration
6. Pharmacokinetics - V/F [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
   Apparent volume of distribution during terminal phase after non-intravenous administration
7. Objective response rate (ORR) [ Time Frame: up to approximately 3 years ]
   Sum of partial response (PR) plus complete response (CR) determined by the Lugano Classification for NHL and by the modified International PCNSL collaborative Group (IPCG) criteria
8. Time to response (TTR) [ Time Frame: up to approximately 3 years ]
   Time from first dose of CC-99282 to the first documentation of response ≥ PR
9. Duration of response (DoR) [ Time Frame: up to approximately 3 years ]
   Time from first documentation of response (≥ PR) to the first documentation of PD or death
10. Progression free survival [ Time Frame: up to approximately 3 years ]
    Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
11. Overall survival [ Time Frame: up to approximately 3 years ]
    Time from first dose of CC-99282 to death from any cause

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
2. Subject has a history of NHL with relapsed or refractory disease
3. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

4. Subjects must have the following laboratory values:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if pegfilgastrim)
   2. Hemoglobin (Hgb) ≥ 8 g/dL
   3. Platelets (plt) ≥ 75 x 109/L without transfusion for 7 days
   4. Serum bilirubin ≤ 1.5 x ULN (upper limit of normal).
   5. AST/SGOT and ALT/SGPT ≤ 2.5X ULN
   6. Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation.
5. Agree to follow the CC-99282 Pregnancy Prevention Plan (PPP)

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has life expectancy ≤ 2 months.
2. Subject has received prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting CC-99282, whichever is shorter.
3. Subject has symptomatic CNS involvement of disease (does not apply to PCNSL subjects in Part B).
4. Persistent diarrhea or malabsorption≥ Grade 2 , despite medical management
5. Subject is on chronic systemic immunosuppressive therapy or corticosteroids (eg, prednisone or equivalent not to exceed 10 mg per day within the last 14 days) or subjects with clinically significant graft-versus-host disease (GVHD).
6. Subject had prior autologous SCT ≤ 3 months prior to starting CC 99282. If subject had prior autologous SCT > 3 months prior to the start of CC-99282, any treatment-related toxicity is unresolved (grade > 1).
7. Subject had prior allogeneic SCT with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99282. If subject had prior allogenic SCT > 6 months prior to the start of CC-99282, any treatment-related toxicity is unresolved (grade > 1).
8. Impaired cardiac function or clinically significant cardiac disease

Contacts and Locations

Contacts

Contact: Associate Director Clinical Trial Disclosure; 1-888-260-1599; clinicaltrialdisclosure@celgene.com

Locations

United States, Florida

H Lee Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 32207

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Canada, Alberta

Cross Cancer Institute University of Alberta; Not yet recruiting

Edmonton, Alberta, Canada, T6G1Z2

Canada, Ontario

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Jewish General Hospital; Not yet recruiting

Montreal, Quebec, Canada, H3T 1E2

France

Centre Hospitalier Lyon-Sud; Recruiting

Pierre-Benite CEDEX, France, 69495

Gustave Roussy; Recruiting

Villejuif CEDEX, France, 94805

Italy

Azienda Ospedaliera Papa Giovanni XXIII; Recruiting

Bergamo, Italy, 24127

Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"; Recruiting

Napoli, Italy, 80131

Spain

Vall d´Hebron University Hospital; Recruiting

Barcelona, Spain, 08035

Fundacion Jimenez Daaz; Recruiting

Madrid, Spain, 28040

Hospital La Paz; Not yet recruiting

Madrid, Spain, 28046

Hospital Universitario Virgen De La Victoria; Not yet recruiting

Malaga, Spain, 29010

Sponsors and Collaborators

Celgene

Investigators

• Study Director: Poliana Patah, MD, PhD; Bristol-Myers Squibb

More Information

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT03930953
• Other Study ID Numbers: CC-99282-NHL-001; U1111-1224-5399 ( Registry Identifier: WHO ); 2018-003235-29 ( EudraCT Number )
• First Posted: April 29, 2019
• Last Update Posted: January 14, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: See Plan Description
• Access Criteria: See Plan Description
• URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• 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; Safety; Efficacy; CC-99282; Rituximab; Relapsed; Refractory

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents