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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04434196
• Other study ID #: CC-99282-CLL-001
• Secondary ID: U1111-1251-42612
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 21, 2020
• Est. completion date: May 13, 2025

Study information

• Verified date: March 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: May 13, 2025
• Est. primary completion date: November 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• CC-99282
CC-99282
• Obinutuzumab
Obinutuzumab

Locations

Country	Name	City	State
Austria	Local Institution - 403	Innsbruck
Austria	Local Institution - 401	Salzburg
Austria	Local Institution - 402	Wien
Canada	Local Institution - 202	Montreal	Quebec
Canada	Local Institution - 201	Toronto	Ontario
Spain	Local Institution - 302	Barcelona
Spain	Local Institution - 301	Madrid
Spain	Local Institution - 306	Madrid
Spain	Local Institution - 304	Pamplona
Spain	Local Institution - 303	Salamanca
Spain	Local Institution - 305	Valencia
United States	Local Institution - 106	Boston	Massachusetts
United States	Local Institution - 104	Columbus	Ohio
United States	Local Institution - 107	Dallas	Texas
United States	Local Institution - 101	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	Number of subjects with a DLT	Up to Cycle 2 Day 14 (each cycle is 28 days)
Primary	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
Primary	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	Pharmacokinetics - Cmax	Maximum observed plasma concentration	Up to Cycle 2 Day 14 (each cycle is 28 days)
Secondary	Pharmacokinetics - AUC	Area under the plasma concentration-time curve	Up to Cycle 2 Day 14 (each cycle is 28 days)
Secondary	Pharmacokinetics - Tmax	Time to Cmax	Up to Cycle 2 Day 14 (each cycle is 28 days)
Secondary	Pharmacokinetics - T-HALF	Terminal-phase elimination half-life	Up to Cycle 2 Day 14 (each cycle is 28 days)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Duration of response (DoR)	Time from first documentation of response (= PR) to the first documentation of PD or death	Up to approximately 3 years
Secondary	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
Secondary	Overall survival	Time from first dose of CC-99282 to death from any cause	Up to approximately 3 years
Secondary	Complete response with incomplete marrow recovery (CRi)	As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Secondary	Nodular partial response (nPR)	As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Secondary	Partial response (PR)	As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years
Secondary	Partial response with lymphocytosis (PRL)	As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria	Up to approximately 3 years

External Links

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