Study of CC-122 to Evaluate the Safety, Tolerability, and Effectiveness for Patients With Advanced Solid Tumors, Non-Hodgkin's Lymphoma, or Multiple Myeloma
|ClinicalTrials.gov Identifier: NCT01421524|
Recruitment Status : Active, not recruiting
First Posted : August 23, 2011
Last Update Posted : March 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma Lymphoma, Large B-Cell, Diffuse Pleiotropic Pathway Modifier Glioblastoma Lymphoma Primary Central Nervous System Lymphoma||Drug: CC-122||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||254 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1a/1b, Multi-center, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Pleiotropic Pathway Modifier CC-122 Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin's Lymphoma, or Multiple Myeloma.|
|Actual Study Start Date :||September 19, 2011|
|Estimated Primary Completion Date :||October 29, 2018|
|Estimated Study Completion Date :||October 29, 2018|
Experimental: CC-122 MM-2
A new MM cohort (MM-2) will be enrolled in order to evaluate tolerability, safety and preliminary efficacy of the CC-122 formulated capsule given on an intermittent schedule (5/7 days per week) in 2 parallel dose escalation cohorts (MM-2a and MM-2b, respectively) (DEX) in Pomalidomide naïve subjects
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).
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 .
Experimental: Primary Central Nervous System Lymphoma (PCNSL)
During dose expansion of selected intermittent schedules, an additional cohort of up to 10 subjects with PCNSL will also be explored at the same dose and schedule as DLBCL to confirm some safety and preliminary efficacy signal
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.
- Dose‐Limiting Toxicity (DLT) [ Time Frame: Up to approximately Day 28 ]
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.
- Pharmacokinetics- Cmax [ Time Frame: Up to day 22 ]Maximum observed concentration in plasma (Cmax)
- Pharmacokinetics- AUC [ Time Frame: Up to day 22 ]Area under the concentration-time curve
- Pharmacokinetics- tmax [ Time Frame: Up to day 22 ]Time to maximum concentration
- Pharmacokinetics- t1/2 [ Time Frame: Up to day 22 ]Terminal half-life
- Pharmacokinetics- CL/F [ Time Frame: Up to day 22 ]Apparent total body clearance
- Pharmacokinetics- Vz/F [ Time Frame: Up to day 22 ]Apparent volume of distribution
- Non-tolerated dose (NTD) [ Time Frame: Up to day 28 ]Is defined as the dose level at which ≥2 out of 6 evaluable subjects in any dose cohort with DLT.
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to day 28 ]Is defined as the last dose level below the NTD with ≤1 out of 6 evaluable subjects with DLT) during Cycle (C) 1.
- Response Rate [ Time Frame: up to approximately 6 months ]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)
- Tissue concentration of CC-122 [ Time Frame: up to approximately 6 months ]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.
- 6-month progression free survival (PFS) rate for GBM chort [ Time Frame: Up to approximately 6 months ]The primary efficacy variable for GBM chohort is 6-month progression free survival (PFS).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01421524
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|Study Director:||Michael Pourdehnad, MD||Celgene Corporation|