Study of CC-122 to Evaluate the Safety, Tolerability, and Effectiveness for Patients With Advanced Solid Tumors, Non-Hodgkin's Lymphoma, or Multiple Myeloma
The main purpose of this first 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.
Diffuse Large B-cell Lymphoma
Mantle Cell Lymphoma
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2, Multi-center, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Pleiotropic Pathway Modifier (PPM) CC-122 Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin's Lymphoma, or Multiple Myeloma.|
- Dose-Limiting Toxicity [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]
A Dose-limiting toxicity (DLT) will be any clinically relevant drug related toxicity starting within 28 days from the first dose (Cycle1) that is > grade 3 (according to NCI CTCAE v 4.0 criteria) as defined below:
- AE > grade 3 except for alopecia or grade 3 acneiform or maculopapular skin rash lasting <4 days or grade 3 diarrhea or vomiting lasting <72h
- a laboratory abnormality that is > grade 3
- febrile neutropenia
- grade 4 neutropenia for >7 days
- grade 4 thrombocytopenia for > 24 hours
- grade 3 or 4 thrombocytopenia with clinically significant bleeding
- grade 4 liver function tests (LFTS) or grade 3 ALT with > grade 2 bilirubin (other grade 3 LFTs due to tumor progression in liver are not DLT). For DLT, transaminase values must be assessed as at least possibly treatment-related DLT AND >1 grade above baseline AND/OR clinically relevant per treating investigator
- An adverse event necessitating dose reduction during Cycle 1.
- Non Tolerated Dose [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]Non Tolerated Dose (NTD) - when two or more out of six evaluable subjects in a cohort experience drug related dose limiting toxicities during Cycle 1. When the NTD is established, dose escalation will stop and no more patients will be entered at the NTD level.
- Maximum Tolerated Dose [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]Maximum Tolerated Dose (MTD) - the highest dose level below the non-tolerated dose with zero or one out of six evaluable subjects experiencing a dose limiting toxicity during Cycle 1
- Maximum Observed Concentration [ Time Frame: Up to Day 16 ] [ Designated as safety issue: No ]Maximum observed concentration for CC-122 Maximum observed concentration for CC-122 when administered in an intermittent schedule at a dose of 4 or 5mg of CC-122 administered 5 out of 7 days per week) in the DLBCL-2 cohort or 4 or 5mg administered 21 out of 28 days in the DLBCL-2 cohort. Maximum observed concentration for CC-122 when administered in a continuous schedule of 4 mg daily or higher of CC-122 administered daily continuously in the GBM-2 cohort
- Time to concentration [ Time Frame: Up to Day 16 ] [ Designated as safety issue: No ]Time to first maximum concentration for CC-122 Time to first maximum observed concentration of CC-122 after 8-10 doses in the intermittent schedule 5/7 (DLBCL-2 cohort), or after 15 doses in the daily schedule 21/28 days (DLBCL-2 cohort) or after 15 doses administered daily continuously (GBM-2 cohort)
- Terminal half-life [ Time Frame: Up to Day 16 ] [ Designated as safety issue: No ]Terminal half-life for CC-122
- Apparent Total Body Clearance [ Time Frame: Up to Day 16 ] [ Designated as safety issue: No ]Apparent total body clearance for CC-122
- Apparent Volume Distribution [ Time Frame: Up to Day 16 ] [ Designated as safety issue: No ]Apparent volume distribution of CC-122
- Creatinine Clearance [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]Creatinine clearance
- CC-122 in urine [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]The amount of CC-122 excreted in the urine
- Response Rate [ Time Frame: Up to 1 Year ] [ Designated as safety issue: No ]The response rate of each tumor types based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), International Workshop Criteria (IWC) for NHL, International Uniform Response Criteria for Multiple Myeloma (IURC), or Responses Assessment for Neuro-Oncology (RANO) working group for Glioblastama multiforme (GBM)
- Determine Central Nervous System (CNS) penetration of CC-122 following the administration of CC-122 [ Time Frame: C1 Days 15 +/- 7 days8, 15, and 22 ] [ Designated as safety issue: No ]Tissue concentration of CC-122 in salvage resection specimens from subjects with GBM or in CSF specimens from subjects undergoing lumbar puncture
- Determination of tumor penetration of CC-122 following the administration of CC-122 in patients enrolled in the expansion phase [ Time Frame: C1 Days15 +/- 7 days (between day 8 and 22 ] [ Designated as safety issue: No ]Tissue concentration of CC-122 in tumor biopsies of patients with DLBCL
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Experimental: CC-122 HCL
Cohorts will receive 3 mg or lower dose of CC-122 administered orally for 28 days in 28 day cycles until disease progression, unacceptable toxicity, or subject/physician decision to withdraw
Dose escalation on an intermittent schedule may occur in parallel with evaluation of the recommended 28 out of 28 day dose in Part B.
Experimental: CC-122- DLBCL-2
A new DLBCL cohort (DLBCL-2) in order to evaluate intermittent schedules of CC-122 (5 continuous days out of 7 days per week [5/7 days] and/or 21 continuous days out of 28 days per cycle [21/28 days]). Doses to be explored include 4 mg and 5 mg on an intermittent schedule using the 3+3 design described in Part A in order to establish an MTD for the intermittent dosing schedules. Following dose escalation, one or more intermittent dosing schedules may be expanded at or below the new intermittent schedule MTD in at least 20 total subjects per dosing schedule.
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.
Experimental: CC-122- GBM-2
A new GBM cohort (GBM-2) in order to evaluate doses of CC-122 above the 3 mg QD MTD determined in all comers in Part A. CC-122 dose will increase in 1 mg increments starting with 4 mg daily on a continuous schedule using the 3+3 design described in Part A in order to establish an MTD specific for GBM subjects. Following dose escalation, the cohort will be expanded at or below the new MTD in up to 20 total subjects.
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 .
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01421524
|Contact: Associate Director, Clinical Trial Disclosurefirstname.lastname@example.org|
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