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

Celgene

Status and phase: Completed; Phase 1

Conditions: Lymphoma, Non-Hodgkin

Treatments: Drug: Obinutuzumab; Drug: CC-99282

Study type: Interventional

Funder types: Industry

Identifiers

NCT04434196

CC-99282-CLL-001

U1111-1251-4261 (Other Identifier)

2019-003228-18 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

16 participants in 1 patient group

CC-99282 + obinutuzumab

Experimental group

Description:

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.

Treatment:

Drug: CC-99282

Drug: Obinutuzumab