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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)

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ClinicalTrials.gov Identifier: NCT03930953
Recruitment Status : Recruiting
First Posted : April 29, 2019
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

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




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



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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. 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).
  5. Subject had prior autologous SCT ≤ 3 months prior to starting CC 99282 and any treatment-related toxicity is unresolved (grade > 1).
  6. Subject had prior allogeneic SCT with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99282 and any treatment-related toxicity is unresolved (grade > 1).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03930953


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

Locations
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United States, Florida
H Lee Moffitt Cancer Center Not yet 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, Ontario
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
France
Centre Hospitalier Lyon-Sud Recruiting
Pierre-Benite CEDEX, France, 69495
Gustave Roussy Recruiting
Villejuif CEDEX, France, 94805
Italy
Azienda Ospedaliera Papa Giovanni XXIII Not yet recruiting
Bergamo, Italy, 24127
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" Not yet recruiting
Napoli, Italy, 80131
Spain
Vall d´Hebron University Hospital Recruiting
Barcelona, Spain, 08035
Fundacion Jimenez Daaz Recruiting
Madrid, Spain, 28040
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Aparna Mani, MD, PhD Celgene Corporation

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03930953     History of Changes
Other Study ID Numbers: CC-99282-NHL-001
U1111-1224-5399 ( Registry Identifier: WHO )
2018-003235-29 ( EudraCT Number )
First Posted: April 29, 2019    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
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/

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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:
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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