Description:
CC-99282-CLL-001 study is a Phase IB dose escalation and expansion clinical study of CC-99282
administered in combination with Obinutuzumab in subjects with relapsed or refractory Chronic
Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Title
- Brief Title: A Safety and Preliminary Efficacy Study of CC-99282 in Combination With Obinutuzumab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Official Title: A Phase 1B, Multicenter, Open-label Study to Determine the Safety, Pharmacokinetics and Preliminary Efficacy of CC-99282 in Combination With Obinutuzumab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
CC-99282-CLL-001
- SECONDARY ID:
U1111-1251-4261
- SECONDARY ID:
2019-003228-18
- NCT ID:
NCT04434196
Conditions
Interventions
Drug | Synonyms | Arms |
---|
CC-99282 | | CC-99282 + obinutuzumab |
Obinutuzumab | | CC-99282 + obinutuzumab |
Purpose
CC-99282-CLL-001 study is a Phase IB dose escalation and expansion clinical study of CC-99282
administered in combination with Obinutuzumab in subjects with relapsed or refractory Chronic
Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Detailed Description
All eligible subjects must be relapsed or refractory to at least 2 prior lines of therapy,
one of which must have included an inhibitor of B-cell receptor signaling (approved Bruton's
tyrosine kinase inhibitor [BTKi] or Phosphoinositide 3-kinase inhibitor [PI3Ki]) or
venetoclax. The dose escalation (Part A) will evaluate the safety, tolerability, and PK of
escalating doses of CC-99282 given in combination with intravenous obinutuzumab to determine
the MTD and RP2D of CC-99282 when given in combination with obinutuzumab.The dose expansion
(Part B) may occur at the MTD established in the dose escalation phase, or at an alternative
tolerable dosing schedule, based on review of safety, PK and PD data from Part A.
Trial Arms
Name | Type | Description | Interventions |
---|
CC-99282 + obinutuzumab | Experimental | Escalating doses of CC-99282 administered orally once daily on intermittent schedules with obinutuzumab IV infusion 1000 mg up to 2 years in Part A. CC-99282 administered orally once daily at MTD or alternative tolerating dosing schedule with obinutuzumab IV infusion 1000 mg up to 2 years in Part B. | |
Eligibility Criteria
Inclusion Criteria:
1. Subject is ≥18 years of age
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
3. Must have a documented diagnosis of CLL/SLL requiring treatment (IwCLL Guidelines for
the Diagnosis and Treatment of CLL). In addition presence of clinically measurable
disease determined by at least one of the factors listed:
- nodal lesion that measures ≥ 1.5 cm in longest dimension (LD) and ≥ 1.0 cm in
longest perpendicular dimension (LPD), or
- spleen that measures ≥ 14 cm in longest vertical dimension (LVD) with a minimum
of 2 cm enlargement, or
- liver that measures ≥ 20 cm in LVD with a minimum of 2 cm enlargement, or
- peripheral blood B lymphocyte count > 5000/uL
4. All eligible subjects must be relapsed after or be refractory to >2 prior lines of
therapy one of which must have included an approved BTK inhibitor.
5. Must meet the following laboratory parameters:
1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if
secondary to bone marrow involvement by disease.
2. Platelet count ≥ 100,000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x
109/L) if secondary to bone marrow involvement by disease.
3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0
x upper limit of normal (ULN).
4. Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.
5. Calculated creatinine clearance of ≥ 60 ml/min.
Exclusion Criteria:
1. Presence of any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.
2. Prior allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of
signing the ICD. Subjects who received allogeneic SCT ≥ 12 months before signing the
ICD may be eligible provided there is no ongoing graft-versus-host disease and no
ongoing immune suppression therapy.
3. Subject has received prior CAR-T or other T-cell targeting treatment (approved or
investigational) ≤ 4 weeks prior to starting CC-99282.
4. Subject has received prior therapy with CRBN-modulating drug (eg, lenalidomide,
avadomide/CC-122, pomalidomide) ≤ 4 weeks prior to starting CC-99282.
5. History of second malignancies with life expectancy of ≤ 2 years or requirement of
therapy that would confound study results.
6. Peripheral neuropathy ≥ Grade 2.
7. History of hypersensitivity to lenalidomide, pomalidomide, thalidomide.
8. Impaired cardiac function or clinically significant cardiac disease.
9. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.
10. Active disease transformation (ie, Richter's Syndrome)
11. Uncontrolled/active autoimmune hemolytic anemia or thrombocytopenia
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 Cycle 2 Day 14 (each cycle is 28 days) |
Safety Issue: | |
Description: | Number of subjects with a DLT |
Secondary Outcome Measures
Measure: | Pharmacokinetics - Cmax |
Time Frame: | Up to Cycle 2 Day 14 (each cycle is 28 days) |
Safety Issue: | |
Description: | Maximum observed plasma concentration |
Measure: | Pharmacokinetics - AUC |
Time Frame: | Up to Cycle 2 Day 14 (each cycle is 28 days) |
Safety Issue: | |
Description: | Area under the plasma concentration-time curve |
Measure: | Pharmacokinetics - Tmax |
Time Frame: | Up to Cycle 2 Day 14 (each cycle is 28 days) |
Safety Issue: | |
Description: | Time to Cmax |
Measure: | Pharmacokinetics - t1/2 |
Time Frame: | Up to Cycle 2 Day 14 (each cycle is 28 days) |
Safety Issue: | |
Description: | Terminal-phase elimination half-life |
Measure: | Pharmacokinetics - CL/F |
Time Frame: | Up to Cycle 2 Day 14 (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: | Up to Cycle 2 Day 14 (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 complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), partial response (PR), partial response with lymphocytosis (PRL) determined by iwCLL criteria |
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 |
Measure: | Complete response with incomplete marrow recovery (CRi) |
Time Frame: | Up to approximately 3 years |
Safety Issue: | |
Description: | As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria |
Measure: | Nodular partial response (nPR) |
Time Frame: | Up to approximately 3 years |
Safety Issue: | |
Description: | As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria |
Measure: | Partial response (PR) |
Time Frame: | Up to approximately 3 years |
Safety Issue: | |
Description: | As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria |
Measure: | Partial response with lymphocytosis (PRL) |
Time Frame: | Up to approximately 3 years |
Safety Issue: | |
Description: | As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Celgene |
Trial Keywords
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Safety
- Efficacy
- CC-99282
- Obinutuzumab
- Relapsed
- Refractory
Last Updated
July 13, 2021