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 | Completed Phase 1 FDA Drug

• 3 other identifiers: CC-99282-CLL-001U1111-1251-42612019-003228-18
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 15

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.

Conditions

Lymphoma, Non-Hodgkin

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity (DLT)

  Number of subjects with a DLT

  Up to Cycle 2 Day 14 (each cycle is 28 days)

• Maximum tolerated dose (MTD)

  The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability

  Up to Cycle 2 Day 14 (each cycle is 28 days

• Adverse Events (AEs)

  An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

  From first subjects first visit until 28 days after last subject discontinued study treatment

Secondary Outcomes (14)

• Pharmacokinetics - Cmax

  Up to Cycle 2 Day 14 (each cycle is 28 days)

• Pharmacokinetics - AUC

  Up to Cycle 2 Day 14 (each cycle is 28 days)

• Pharmacokinetics - Tmax

  Up to Cycle 2 Day 14 (each cycle is 28 days)

• Pharmacokinetics - T-HALF

  Up to Cycle 2 Day 14 (each cycle is 28 days)

• Pharmacokinetics - CLT/F

  Up to Cycle 2 Day 14 (each cycle is 28 days)

Study Arms (1)

CC-99282 + obinutuzumab

EXPERIMENTAL

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.

Drug: CC-99282; Drug: Obinutuzumab

Interventions

CC-99282 DRUG

CC-99282

CC-99282 + obinutuzumab

Obinutuzumab DRUG

Obinutuzumab

CC-99282 + obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 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
• 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.
• Must meet the following laboratory parameters:
• 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).
• 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.
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) \< 3.0 x upper limit of normal (ULN).
• Serum bilirubin \< 1.5 x ULN unless due to Gilbert's syndrome.
• Calculated creatinine clearance of ≥ 60 ml/min.

You may not qualify if:

• Presence of any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• 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.
• Subject has received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to starting CC-99282.
• Subject has received prior therapy with CRBN-modulating drug (eg, lenalidomide, avadomide/CC-122, pomalidomide) ≤ 4 weeks prior to starting CC-99282.
• History of second malignancies with life expectancy of ≤ 2 years or requirement of therapy that would confound study results.
• Peripheral neuropathy ≥ Grade 2.
• History of hypersensitivity to lenalidomide, pomalidomide, thalidomide.
• Impaired cardiac function or clinically significant cardiac disease.
• Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.
• Active disease transformation (ie, Richter's Syndrome)
• Uncontrolled/active autoimmune hemolytic anemia or thrombocytopenia

Sponsors & Collaborators

• Celgene: lead

Study Sites (15)

Local Institution - 106

Boston, Massachusetts, 02215, United States

Location

Local Institution - 104

Columbus, Ohio, 43210, United States

Location

Local Institution - 101

Portland, Oregon, 97201-3098, United States

Location

Local Institution - 107

Dallas, Texas, 75390, United States

Location

Local Institution - 403

Innsbruck, 6020, Austria

Location

Local Institution - 401

Salzburg, 5020, Austria

Location

Local Institution - 402

Vienna, 1090, Austria

Location

Local Institution - 201

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 202

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 304

Pamplona, Navarre, 31008, Spain

Location

Local Institution - 302

Barcelona, 08035, Spain

Location

Local Institution - 306

Madrid, 28027, Spain

Location

Local Institution - 301

Madrid, 28041, Spain

Location

Local Institution - 303

Salamanca, 37007, Spain

Location

Local Institution - 305

Valencia, 46010, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 16, 2020
• Study Start: December 21, 2020
• Primary Completion: May 21, 2024
• Study Completion: May 21, 2024
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

ES (6); US (4); AU (3); CA (2)