A Study of CC-122 to Assess the Safety and Tolerability in Japanese Patients With Advanced Solid Tumors and Non-Hodgkin's Lymphoma (NHL)

NCT02509039 | Terminated Phase 1 Results

• 1 other identifier: CC-122-ST-002
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Conditions

Lymphoma, Non-Hodgkin

Keywords

CC-122; Phase1; solid tumor; non-Hodgkin's lymphom

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs: * Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting \> 7 days, Grade 4 thrombocytopenia lasting \> 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding * Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs * Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period

  From first dose up to at least 28 days (Cycle 1)

• Maximum Tolerated Dose (MTD)

  The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D). MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03

  From first dose up to at least 28 days (Cycle 1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03

  From first dose to 28 days post last dose of investigational product (Up to approximately 92 months)

• Pharmacokinetic Parameters of CC-122: AUC0-t

  Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: AUCtau

  Area under the plasma concentration time-curve during a dosing interval (AUCtau)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: Cmax

  Peak (maximum) plasma concentration (Cmax)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: Tmax

  Time to maximum plasma concentration (Tmax)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: t1/2

  Terminal half-life of CC-122 (t1/2)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: CL/F

  Apparent clearance (CL/F)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Pharmacokinetic Parameters of CC-122: Vz/F

  Apparent volume of distribution (Vz/F)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

• Accumulation Index of CC-122

  Accumulation Index defined as AUCtau (Cycle 1 Day 10, 11 or 12)/AUCtau (Cycle 1 Day 1)

  0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)

Secondary Outcomes (2)

• Best Overall Response (BOR)

  From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)

• Duration of Response (DoR)

  From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)

Study Arms (1)

CC-122

EXPERIMENTAL

CC-122 is administered orally, on a 5 continuous days out of 7 days per week intermittent dosing schedule.

Drug: CC-122

Interventions

CC-122 DRUG

5 continuous days out of 7 days per week intermittent dosing

CC-122

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted
• years or older, with histological or cytological confirmation of advanced solid tumors or Non-Hodgkin's Lymphoma (NHL), including those who have progressed on standard anticancer therapy or for whom no other conventional therapy exists
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 for all tumors
• Subjects must have the following laboratory values:
• ・Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion
• Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion
• Potassium within normal limits or correctable with supplements
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are present
• Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin \>1.5 x ULN and ≤ 2 x ULN may be enrolled if agreed to by the sponsor
• Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min
• Negative serum pregnancy test in females of childbearing potential as per the CC-122 Pregnancy Prevention Rist Management Plan
• Able to adhere to the study visit schedule and other protocol requirements
• Must adhere to the Pregnancy Prevention Rist Management Plan

You may not qualify if:

• Subjects with primary central nervous system (CNS) malignancies or symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed
• Known acute or chronic pancreatitis
• Any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2
• Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Left Ventricular Ejection Fraction (LVEF) \< 45% as determined by Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)
• Complete left bundle branch, or bifascicular block
• Congenital long QT syndrome
• Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation
• QTcF \> 460 msec on screening electrocardiogram (ECG) (mean of triplicate recordings)
• Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122
• Troponin-T value \>0.4 ng/mL or Brain Natriuretic Peptide (BNP) \>300 pg/mL Subjects with baseline troponin-T \>ULN or BNP \>100 pg/mL are eligible but must and optimization of cardioprotective therapy.
• Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)
• Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists will be allowed for subjects with metastatic prostate cancer
• Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative side effects

Sponsors & Collaborators

• Celgene: lead

Study Sites (3)

Local Institution - 002

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 003

Chikusa-ku, 464-8681, Japan

Location

Local Institution - 001

Kashiwa, 277-8577, Japan

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: July 27, 2015
• Study Start: September 2, 2015
• Primary Completion: May 9, 2023
• Study Completion: May 9, 2023
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-04

Locations

JP (3)