Clinical Trials /

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

NCT04434196

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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: Phase 1b Study to Determine the Safety, Pharmacokinetics, and Preliminary Efficacy of the Combination of CC-99282 and 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

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
CC-99282CC-99282 + obinutuzumab
ObinutuzumabCC-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

NameTypeDescriptionInterventions
CC-99282 + obinutuzumabExperimentalEscalating 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.
  • CC-99282
  • Obinutuzumab

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:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Safety
  • Efficacy
  • CC-99282
  • Obinutuzumab
  • Relapsed
  • Refractory

Last Updated

June 12, 2020