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).
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 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).
Clinical Trial IDs
- ORG STUDY ID:
CC-99282-NHL-001
- SECONDARY ID:
U1111-1224-5399
- SECONDARY ID:
2018-003235-29
- NCT ID:
NCT03930953
Conditions
Interventions
Drug | Synonyms | Arms |
---|
CC-99282 | | Administration of CC-99282 |
rituximab | | CC-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
Name | Type | Description | Interventions |
---|
Administration of CC-99282 | Experimental | Escalating doses of CC-99282 administered orally once daily on intermittent schedules up to 2 years. | |
CC-99282 + rituximab | Experimental | 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. | |
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. 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
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
August 20, 2021