Clinical trial NCT04434196: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Keywords: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Safety
Efficacy
CC-99282
Obinutuzumab
Relapsed
Refractory
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2020-06-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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/mm\^3 or ≥ 1000 cells/mm\^3 if secondary to bone marrow involvement by disease, without growth factor support for 7 days (14 days if pegfilgastrim).
   2. Platelet count ≥ 75,000 cells/mm\^3 (100 x 10\^9/L) or ≥ 50,000 cells/mm\^3 (50 x 10\^9/L) if secondary to bone marrow involvement by disease, without transfusion for 7 days.
   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 ICF. Subjects who received allogeneic SCT ≥ 12 months before signing the ICF 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Maximum tolerated dose (MTD)
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days
measure: Adverse Events (AEs)
timeFrame: From first subjects first visit until 28 days after last subject discontinued study treatment
Secondary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Pharmacokinetics - AUC
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Pharmacokinetics - Tmax
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Pharmacokinetics - T-HALF
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Pharmacokinetics - CLT/F
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Pharmacokinetics - Vz/F
timeFrame: Up to Cycle 2 Day 14 (each cycle is 28 days)
measure: Objective response rate (ORR)
timeFrame: Up to approximately 3 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 3 years
measure: Progression free survival
timeFrame: Up to approximately 3 years
measure: Overall survival
timeFrame: Up to approximately 3 years
measure: Complete response with incomplete marrow recovery (CRi)
timeFrame: Up to approximately 3 years
measure: Nodular partial response (nPR)
timeFrame: Up to approximately 3 years
measure: Partial response (PR)
timeFrame: Up to approximately 3 years
measure: Partial response with lymphocytosis (PRL)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Local Institution - 106
state: Massachusetts
city: Columbus
country: United States
facility: Local Institution - 104
state: Ohio
city: Portland
country: United States
facility: Local Institution - 101
state: Oregon
city: Dallas
country: United States
facility: Local Institution - 107
state: Texas
city: Innsbruck
country: Austria
facility: Local Institution - 403
city: Salzburg
country: Austria
facility: Local Institution - 401
city: Wien
country: Austria
facility: Local Institution - 402
city: Toronto
country: Canada
facility: Local Institution - 201
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 202
state: Quebec
city: Pamplona
country: Spain
facility: Local Institution - 304
state: Navarra
city: Barcelona
country: Spain
facility: Local Institution - 302
city: Madrid
country: Spain
facility: Local Institution - 306
city: Madrid
country: Spain
facility: Local Institution - 301
city: Salamanca
country: Spain
facility: Local Institution - 303
city: Valencia
country: Spain
facility: Local Institution - 305
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: