June 16, 2020
January 20, 2021
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.
|Experimental: CC-99282 + obinutuzumab
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.
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
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 firstname.lastname@example.org
United States, Massachusetts
Dana Farber Cancer Institute
United States, New York
Memorial Sloan-Kettering Cancer Center
United States, Ohio
The Ohio State University Comprehensive Cancer Center
United States, Oregon
Oregon Health and Science University
United States, Texas
Southwestern Medical Center- Harold C Simmons Comprehensive Cancer Center
Universitaetsklinik fuer Innere Medizin V
Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien
Princess Margaret Hospital University Health Network
Sir Mortimer B. Davis - Jewish Genl
Hospital Universitario Vall D hebron
Hospital 12 de Octubre
Clinica Universidad de Navarra
Universitario de Salamanca - Hospital Clinico
Hospital Clinico Universitario de Valencia
Study Director: Poliana Patah, MD, PhD Bristol-Myers Squibb