Clinical Trials /

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)

NCT03930953

Description:

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).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • 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).

Clinical Trial IDs

  • ORG STUDY ID: CC-99282-NHL-001
  • SECONDARY ID: U1111-1224-5399
  • SECONDARY ID: 2018-003235-29
  • NCT ID: NCT03930953

Conditions

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
CC-99282Administration of CC-99282
rituximabCC-99282 + rituximab

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Administration of CC-99282ExperimentalEscalating doses of CC-99282 administered orally once daily on intermittent schedules up to 2 years.
  • CC-99282
CC-99282 + rituximabExperimentalCC-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.
  • CC-99282
  • rituximab

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity (DLT)
Time Frame:up to 28 days in Cycle 1
Safety Issue:
Description:Number of subjects with a DLT

Secondary Outcome Measures

Measure:Pharmacokinetics - Cmax
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Maximum observed plasma concentration
Measure:Pharmacokinetics - AUC
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Area under the plasma concentration-time curve
Measure:Pharmacokinetics - Tmax
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Time to Cmax
Measure:Pharmacokinetics - t1/2
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Terminal-phase elimination half-life
Measure:Pharmacokinetics - CL/F
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Apparent total clearance of the drug from plasma after oral administration
Measure:Pharmacokinetics - V/F
Time Frame:Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days)
Safety Issue:
Description:Apparent volume of distribution during terminal phase after non-intravenous administration
Measure:Objective response rate (ORR)
Time Frame:up to approximately 3 years
Safety Issue:
Description: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
Measure:Time to response (TTR)
Time Frame:up to approximately 3 years
Safety Issue:
Description:Time from first dose of CC-99282 to the first documentation of response ≥ PR
Measure:Duration of response (DoR)
Time Frame:up to approximately 3 years
Safety Issue:
Description:Time from first documentation of response (≥ PR) to the first documentation of PD or death
Measure:Progression free survival
Time Frame:up to approximately 3 years
Safety Issue:
Description:Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
Measure:Overall survival
Time Frame:up to approximately 3 years
Safety Issue:
Description:Time from first dose of CC-99282 to death from any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Non-Hodgkin Lymphomas
  • Safety
  • Efficacy
  • CC-99282
  • Rituximab
  • Relapsed
  • Refractory

Last Updated

October 7, 2019