NCT03930953 - Bristol Myers Squibb™

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:Lymphoma, Non-Hodgkin
Intervention/Treatment: Drug: CC-99282
Drug: rituximab
Phase: 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
Estimated Enrollment: 100 participants
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 2019
Estimated Primary Completion Date: June 2023
Estimated Study Completion Date: May 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
Primary Outcome Measures: 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
Primary Outcome Measures: 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. 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
Secondary Outcome Measures: 2. Overall survival [ Time Frame: up to approximately 3 years ]
Time from first dose of CC-99282 to death from any cause
Secondary Outcome Measures: 3. 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
Secondary Outcome Measures: 4. Pharmacokinetics - Cmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
Maximum observed plasma concentration
Secondary Outcome Measures: 5. Pharmacokinetics - AUC [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
Area under the plasma concentration-time curve
Secondary Outcome Measures: 6. Pharmacokinetics - Tmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
Time to Cmax
Secondary Outcome Measures: 7. Pharmacokinetics - t1/2 [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
Terminal-phase elimination half-life
Secondary Outcome Measures: 8. 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
Secondary Outcome Measures: 9. 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
Secondary Outcome Measures: 10. 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
Secondary Outcome Measures: 11. 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

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, California
University of California, Irvine
Orange

United States, Florida
H Lee Moffitt Cancer Center
Tampa

United States, Missouri
Washington University
Saint Louis

United States, New Jersey
Hackensack University Medical Center
Hackensack

United States, Texas
MD Anderson Cancer Center
Houston

Austria
LKH - Universitätsklinikum der PMU Salzburg
Salzburg

Austria
Medical University Vienna
Vienna

Belgium
UZ Antwerpen
Edegem

Belgium
UZ Gent
Leuven

Belgium
UZ Leuven
Leuven

Canada, Alberta
Cross Cancer Institute University of Alberta
Edmonton

Canada, Ontario
Princess Margaret Cancer Centre
Toronto

Canada
McGill University Health Centre MUHC
Montreal

Denmark
Aarhus University Hospital
Aarhus C

Denmark
Rigshospitalet University Hospital
Copenhagen

Denmark
Vejle Hospital
Vejle

France
Hopital Henri Mondor
Creteil

France
Hospital Saint Louis
Paris

France
Centre Hospitalier Lyon-Sud
Pierre-Benite CEDEX

France
Centre Henri Becquerel
Rouen

France
Gustave Roussy
Villejuif CEDEX

Italy
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo

Italy
ASST Grande Ospedale Metropolitano Niguarda, Milano
Milano

Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"
Napoli

Spain
Vall d´Hebron University Hospital
Barcelona

Spain
Fundacion Jimenez Daaz
Madrid

Spain
Hospital La Paz
Madrid

Spain
Hospital Universitario Virgen De La Victoria
Malaga

United Kingdom
Western General Hospital
Edinburgh Scotland

United Kingdom
Clatterbridge Cancer Centre - Liverpool
Liverpool

United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
London

United Kingdom
Southampton General Hospital
Southhampton

Sponsors and Collaborators

Celgene

Investigators

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

More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03930953 History of Changes
Other Study ID Numbers: CC-99282-NHL-001, U1111-1224-5399, 2018-003235-29
First Posted: April 29, 2019 Key Record Dates
Last Update Posted: September 27, 2021
Last Verified: September 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: Refractory
Relapsed
Rituximab
CC-99282 Efficacy
Safety
Non-Hodgkin Lymphomas
Additional relevant MeSH terms: Lymphoma, Non-Hodgkin Lymphoma

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Condition Categories

Clinical Trials of Interest

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)

Study Description

Detailed Description

Study Design

Arms and interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

Criteria

Contacts and Locations

Contacts

Locations

Sponsors and Collaborators

Investigators

More Information

Individual Participant
Data (IPD) Sharing
Statement:

Log In to Bolder Science

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Create an Account

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Condition Categories

Clinical Trials of Interest

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)

Study Description

Detailed Description

Study Design

Arms and interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

Criteria

Contacts and Locations

Contacts

Locations

Sponsors and Collaborators

Investigators

More Information

Individual Participant Data (IPD) Sharing Statement:

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Individual Participant
Data (IPD) Sharing
Statement: