The main purpose of this first in human study with CC-122 is to assess the safety and action of a new class of experimental drug (Pleiotropic Pathway Modulator) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dosing level and regimen for later-stage clinical trials.
This trial is enrolling additional Multiple Myeloma (MM) subjects in a separate cohort defined as MM-2 to evaluate tolerability, safety and preliminary efficacy of CC-122 formulated capsule alone or in combination with DEX on intermittent dosing schedule (5 of 7 days of the week) in Pomalidomide-naïve subjects. Preliminary efficacy data in Multiple Myeloma subjects, warrants further exploration of CC-122 in MM on intermittent schedules to assess if dose intensity and tolerability can be improved. Initially, patients will be treated with oral CC-122 for one month. During this time, various tests (involving blood and urine collections, ECGs, etc) will be performed. Those whose tumors stabilize or regress may continue receiving treatment for as long as they benefit from CC-122. Different dose levels of CC-122 will be tested in a dose-rising study design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
271
CC-122 dose in both arms will increase by 1 mg increments starting with 3 mg 5/7 days using the 3+3 design in dose escalation phase. A dose-level -1, with a starting dose of 2mg, may also be evaluated if the opening dose level is not tolerated. At all dose levels in MM-2b arm, DEX will be combined with CC-122 at a starting dose dependent on the subject's age: for subjects who are ≤ 75 years of age, DEX 40 mg/day will be given on Days 1, 8, 15 and 22 of a 28-day cycle and for subjects who are \> 75 years of age, DEX 20 mg/day will be given on Days 1, 8, 15 and 22 of a 28-day cycle. Approximately 33 subjects will be enrolled in the dose escalation phase (15 in each treatment arm). An additional intermittent schedule of 21/28 days may be evaluated per Safety Review Committee (SRC) decision. Following dose escalation, one or two arms will be expanded at or below the MTD in up to 28 subjects (14 subjects in each arm).
One or more intermittent schedules of CC-122 either given 5 continuous days out of 7 per week (5/7 days) or 21 continuous days out of 28 days per cycle (21/28 days). Following dose escalation, one or more of these intermittent schedules will be evaluated at a starting dose of 4 mg.
Dose escalation on a continous schedule will be evaluated at a starting dose of 4 mg. Specifically, dose levels with 1 mg increments (eg 4mg, 5mg, 6mg etc.) will be evaluated using a 3+3 design as detailed in Part A of the protocol .
Up to 10 subjects with relapsed or refractory PCNSL will be enrolled to a PCNSL cohort to evaluate intermittent schedules of CC-122 and to further explore preliminary signals of efficacy and biomarker hypotheses.
City of Hope Cancer Center
Duarte, California, United States
UCLA Neuro-Oncology Program
Los Angeles, California, United States
UCSF Helen Diller Medical Center at Parnassus Heights
San Francisco, California, United States
University Of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Henry Ford Medical Center - New Center One
Detroit, Michigan, United States
Dose-Limiting Toxicity (DLT)
Dose-limiting toxicities (DLTs) will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE): * A clinically relevant AE that is suspected to be related to CC-122 and starts ≤ 30 days of first dose (Cycle 1) and ≥ grade (Gr) 3 except for Alopecia, Gr3 rash of the acneiform or maculopapular type \< 4 daysduration , Gr 3 diarrhea or vomiting lasting\< 72 hours * Clinically relevant laboratory abnormality suspected to be related to CC-122 and that commences within 30 days of first dose and ≥ Gr3. * Hematological toxicities as follows: Any febrile neutropenia (NP), Gr4 NP \> 7 days, Gr 4 thrombocytopenia \> 24 hours, Any Gr 3/4 thrombocytopenia with clinically significant bleeding. * Gr 4 liver function tests (LFTs) or Gr 3 ALT with ≥ Gr2 bilirubin * Any AE suspected to be CC-122 related and necessitating dose reduction during Cycle 1.
Time frame: Up to approximately Day 28
Pharmacokinetics- Cmax
Maximum observed concentration in plasma (Cmax)
Time frame: Up to day 22
Pharmacokinetics- AUC
Area under the concentration-time curve
Time frame: Up to day 22
Pharmacokinetics- tmax
Time to maximum concentration
Time frame: Up to day 22
Pharmacokinetics- t1/2
Terminal half-life
Time frame: Up to day 22
Pharmacokinetics- CL/F
Apparent total body clearance
Time frame: Up to day 22
Pharmacokinetics- Vz/F
Apparent volume of distribution
Time frame: Up to day 22
Non-tolerated dose (NTD)
Is defined as the dose level at which ≥2 out of 6 evaluable subjects in any dose cohort with DLT.
Time frame: Up to day 28
Maximum Tolerated Dose (MTD)
Is defined as the last dose level below the NTD with ≤1 out of 6 evaluable subjects with DLT) during Cycle (C) 1.
Time frame: Up to day 28
Response Rate
The response rate of each tumor types based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), International Workshop Criteria (IWC) for Non-Hodgkin's Lymphoma (NHL), International Uniform Response Criteria for Multiple Myeloma (IURC), or Responses Assessment for Neuro-Oncology (RANO) working group for Glioblastama multiforme (GBM)
Time frame: up to approximately 6 months
Tissue concentration of CC-122
Tissue concentration of CC-122 in salvage resection specimens from subjects with GBM (CNS primary tumor) or in cerebrospinal fluid (CSF) from subjects undergoing lumbar puncture.
Time frame: up to approximately 6 months
6-month progression free survival (PFS) rate for GBM chort
The primary efficacy variable for GBM chohort is 6-month progression free survival (PFS).
Time frame: Up to approximately 6 months
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Comprehensive Cancer Centers Of Nevada
Las Vegas, Nevada, United States
Rutgers Cancer Institute of New Jersey University
New Brunswick, New Jersey, United States
Mount Sinai Hospital
New York, New York, United States
Local Institution - 020
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
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