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

NCT ID: NCT04434196

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-21
• Study Completion Date: 2024-05-21

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.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CC-99282

Intervention Type: DRUG

CC-99282

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab

Interventions

CC-99282

CC-99282

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 106

Boston, Massachusetts, United States

Local Institution - 104

Columbus, Ohio, United States

Local Institution - 101

Portland, Oregon, United States

Local Institution - 107

Dallas, Texas, United States

Local Institution - 403

Innsbruck, , Austria

Local Institution - 401

Salzburg, , Austria

Local Institution - 402

Vienna, , Austria

Local Institution - 201

Toronto, Ontario, Canada

Local Institution - 202

Montreal, Quebec, Canada

Local Institution - 304

Pamplona, Navarre, Spain

Local Institution - 302

Barcelona, , Spain

Local Institution - 306

Madrid, , Spain

Local Institution - 301

Madrid, , Spain

Local Institution - 303

Salamanca, , Spain

Local Institution - 305

Valencia, , Spain

Countries

United States; Austria; Canada; Spain

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/content/studyconnect/us/en/clinical-trials/NCT04434196.html

BMS Clinical Trial Patient Recruiting

Other Identifiers

U1111-1251-4261

Identifier Type: OTHER

Identifier Source: secondary_id

2019-003228-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-99282-CLL-001

Identifier Type: -

Identifier Source: org_study_id