JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

Studienbeginn:
Dezember 2020

Letztes Update:
20.01.2021

Wirkstoff:
CC-99282, Obinutuzumab

Indikation (Clinical Trials):
Lymphoma, Leukemia, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Celgene

Collaborator:
-

Studienleiter

Poliana Patah, MD, PhD
Study Director
Bristol-Myers Squibb

Kontakt

Associate Director Clinical Trial Disclosure
Kontakt:
Phone: 1-888-260-1599
E-Mail: clinicaltrialdisclosure@celgene.com» Kontaktdaten anzeigen

Studienlocations (3 von 15)

Dana Farber Cancer Institute
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps

Memorial Sloan-Kettering Cancer Center
10021 New York
United StatesNoch nicht rekrutierend» Google-Maps

The Ohio State University Comprehensive Cancer Center
43210 Columbus
United StatesRekrutierend» Google-Maps

Oregon Health and Science University
97201-3098 Portland
United StatesRekrutierend» Google-Maps

Southwestern Medical Center- Harold C Simmons Comprehensive Cancer Center
75390 Dallas
United StatesNoch nicht rekrutierend» Google-Maps

Universitaetsklinik fuer Innere Medizin V
6020 Innsbruck
AustriaNoch nicht rekrutierend» Google-Maps

Landeskrankenhaus Salzburg
5020 Salzburg
AustriaRekrutierend» Google-Maps

Allgemeinen Krankenhaus (AKH) Wien - Medizinische Universitaet Wien
1090 Wien
AustriaRekrutierend» Google-Maps

Princess Margaret Hospital University Health Network
M5G 2M9 Toronto
CanadaRekrutierend» Google-Maps

Sir Mortimer B. Davis - Jewish Genl
H3T 1E2 Montreal
CanadaNoch nicht rekrutierend» Google-Maps

Hospital Universitario Vall D hebron
08035 Barcelona
SpainRekrutierend» Google-Maps

Hospital 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps

Clinica Universidad de Navarra
31008 Pamplona
SpainRekrutierend» Google-Maps

Universitario de Salamanca - Hospital Clinico
37007 Salamanca
SpainRekrutierend» Google-Maps

Hospital Clinico Universitario de Valencia
46010 Valencia
SpainRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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/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

Studien-Rationale

Primary outcome:

1. Dose Limiting Toxicity (DLT) (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Number of subjects with a DLT

2. Maximum tolerated dose (MTD) (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days):
The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability

3. Adverse Events (AEs) (Time Frame - From first subjects first visit until 28 days after last subject discontinued study treatment):
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.

Secondary outcome:

1. Pharmacokinetics - Cmax (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Maximum observed plasma concentration

2. Pharmacokinetics - AUC (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Area under the plasma concentration-time curve

3. Pharmacokinetics - Tmax (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Time to Cmax

4. Pharmacokinetics - t1/2 (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Terminal-phase elimination half-life

5. Pharmacokinetics - CL/F (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Apparent total clearance of the drug from plasma after oral administration

6. Pharmacokinetics - V/F (Time Frame - Up to Cycle 2 Day 14 (each cycle is 28 days)):
Apparent volume of distribution during terminal phase after non-intravenous administration

7. Objective response rate (ORR) (Time Frame - Up to approximately 3 years):
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

8. Duration of response (DoR) (Time Frame - Up to approximately 3 years):
Time from first documentation of response (≥ PR) to the first documentation of PD or death

9. Progression free survival (Time Frame - Up to approximately 3 years):
Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause

10. Overall survival (Time Frame - Up to approximately 3 years):
Time from first dose of CC-99282 to death from any cause

11. Complete response with incomplete marrow recovery (CRi) (Time Frame - Up to approximately 3 years):
As assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

12. Nodular partial response (nPR) (Time Frame - Up to approximately 3 years):
As assessed by iwCL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

13. Partial response (PR) (Time Frame - Up to approximately 3 years):
As assessed by iwC and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

14. Partial response with lymphocytosis (PRL) (Time Frame - Up to approximately 3 years):
As assessed by iwCLL and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

Geprüfte Regime

CC-99282:
CC-99282
Obinutuzumab:
Obinutuzumab

Quelle: ClinicalTrials.gov

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