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, Multicentre, 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

Summary:

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 Description

Primary Outcome Measures:

  • Dose Limiting Toxicity (DLT) [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Number of subjects with a DLT
  • Maximum tolerated dose (MTD) [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days ]The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability
  • Adverse Events (AEs) [ Time Frame: From first subjects first visit until 28 days after last subject discontinued study treatment ]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.

  • Secondary Outcome Measures:
  • Pharmacokinetics - Cmax [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Maximum observed plasma concentration
  • Pharmacokinetics - AUC [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Area under the plasma concentration-time curve
  • Pharmacokinetics - Tmax [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Time to Cmax
  • Pharmacokinetics - t1/2 [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Terminal-phase elimination half-life
  • Pharmacokinetics - CL/F [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Apparent total clearance of the drug from plasma after oral administration
  • Pharmacokinetics - V/F [ Time Frame: Up to Cycle 2 Day 14 (each cycle is 28 days) ]Apparent volume of distribution during terminal phase after non-intravenous administration
  • Objective response rate (ORR) [ Time Frame: Up to approximately 3 years ]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
  • 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
  • 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
  • Overall survival [ Time Frame: Up to approximately 3 years ]Time from first dose of CC-99282 to death from any cause
  • Complete response with incomplete marrow recovery (CRi) [ Time Frame: Up to approximately 3 years ]As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • Nodular partial response (nPR) [ Time Frame: Up to approximately 3 years ]As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • Partial response (PR) [ Time Frame: Up to approximately 3 years ]As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • Partial response with lymphocytosis (PRL) [ Time Frame: Up to approximately 3 years ]As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • View this trial on ClinicalTrials.gov

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    Resources

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