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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Obinutuzumab; Drug: CC-99282

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Local Institution - 403
  • Salzburg, Austria, 5020
    • Local Institution - 401
  • Wien, Austria, 1090
    • Local Institution - 402
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 201
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 202
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 302
  • Madrid, Spain, 28041
    • Local Institution - 301
  • Madrid, Spain, 28027
    • Local Institution - 306
  • Pamplona, Spain, 31008
    • Local Institution - 304
  • Salamanca, Spain, 37007
    • Local Institution - 303
  • Valencia, Spain, 46010
    • Local Institution - 305
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 106
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Local Institution - 104
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Local Institution - 101
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 107

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Obinutuzumab; Obinutuzumab; Drug: CC-99282; CC-99282

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Maximum observed plasma concentration	Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - AUC	Area under the plasma concentration-time curve	Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - Tmax	Time to Cmax	Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - T-HALF	Terminal-phase elimination half-life	Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - CLT/F	Apparent total clearance of the drug from plasma after oral administration	Up to Cycle 2 Day 14 (each cycle is 28 days)
Pharmacokinetics - Vz/F	Apparent volume of distribution during terminal phase after non-intravenous administration	Up to Cycle 2 Day 14 (each cycle is 28 days)
Objective response rate (ORR)	Sum of complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), partial response (PR), partial response with lymphocytosis (PRL) determined by iwCLL criteria	Up to approximately 3 years
Duration of response (DoR)	Time from first documentation of response (≥ PR) to the first documentation of PD or death	Up to approximately 3 years
Progression free survival	Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause	Up to approximately 3 years
Overall survival	Time from first dose of CC-99282 to death from any cause	Up to approximately 3 years
Complete response with incomplete marrow recovery (CRi)	As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Nodular partial response (nPR)	As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Partial response (PR)	As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Partial response with lymphocytosis (PRL)	As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Celgene

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Anticipated): November 15, 2024
• Study Completion (Anticipated): May 13, 2025

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Relapsed; Refractory; Obinutuzumab; CC-99282; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab
• Other Study ID Numbers: CC-99282-CLL-001; U1111-1251-4261 (Other Identifier: WHO); 2019-003228-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No