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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
CC-99282
Obinutuzumab
Local Institution - 106
Boston, Massachusetts, United States
Local Institution - 104
Columbus, Ohio, United States
Local Institution - 101
Portland, Oregon, United States
Dose Limiting Toxicity (DLT)
Number of subjects with a DLT
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Maximum tolerated dose (MTD)
The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days
Adverse Events (AEs)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
Time frame: From first subjects first visit until 28 days after last subject discontinued study treatment
Pharmacokinetics - Cmax
Maximum observed plasma concentration
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - AUC
Area under the plasma concentration-time curve
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - Tmax
Time to Cmax
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - T-HALF
Terminal-phase elimination half-life
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Local Institution - 107
Dallas, Texas, United States
Local Institution - 403
Innsbruck, Austria
Local Institution - 401
Salzburg, Austria
Local Institution - 402
Vienna, Austria
Local Institution - 201
Toronto, Ontario, Canada
Local Institution - 202
Montreal, Quebec, Canada
Local Institution - 304
Pamplona, Navarre, Spain
...and 5 more locations
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - CLT/F
Apparent total clearance of the drug from plasma after oral administration
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - Vz/F
Apparent volume of distribution during terminal phase after non-intravenous administration
Time frame: Up to Cycle 2 Day 14 (each cycle is 28 days)
Objective response rate (ORR)
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
Time frame: Up to approximately 3 years
Duration of response (DoR)
Time from first documentation of response (≥ PR) to the first documentation of PD or death
Time frame: Up to approximately 3 years
Progression free survival
Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
Time frame: Up to approximately 3 years
Overall survival
Time from first dose of CC-99282 to death from any cause
Time frame: Up to approximately 3 years
Complete response with incomplete marrow recovery (CRi)
As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Time frame: Up to approximately 3 years
Nodular partial response (nPR)
As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Time frame: Up to approximately 3 years
Partial response (PR)
As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Time frame: Up to approximately 3 years
Partial response with lymphocytosis (PRL)
As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Time frame: Up to approximately 3 years