Study of CC-122 to Evaluate the Safety, Tolerability, and Effectiveness for Patients With Advanced Solid Tumors, Non-Hodgkin's Lymphoma, or Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01421524
First received: August 19, 2011
Last updated: April 13, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Non-Hodgkin's Lymphoma
Multiple Myeloma
Glioblastoma Multiforme
Oligodendroglioma
Hepatocellular Carcinoma
Diffuse Large B-cell Lymphoma
Mantle Cell Lymphoma
Drug: CC-122
Phase 1

Study Type: Interventional
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 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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:

    1. 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
    2. a laboratory abnormality that is > grade 3
    3. febrile neutropenia
    4. grade 4 neutropenia for >7 days
    5. grade 4 thrombocytopenia for > 24 hours
    6. grade 3 or 4 thrombocytopenia with clinically significant bleeding
    7. 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
    8. 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 160
Study Start Date: August 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: CC-122
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.
Drug: CC-122
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.
Drug: CC-122
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 .

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults with histologically or cytologically-confirmed Non-Hodgkin Lymphoma, Multiple Myeloma or advanced solid tumors (limited to the tumor types below) who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no standard anticancer therapy exists.
  2. DLBCL (Diffuse large B-cell lymphoma) subjects must have relapsed within 12 months of the start of the last cytotoxic chemotherapy including primary refractory disease.
  3. Adequate organ function
  4. Must have disease that is objectively measurable.
  5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2 (except 0-1 in Hepatocellular Carcinoma and Diffuse Large B-cell Lymphoma)
  6. Archival tumor samples and screening and on treatment biopsies. (archival not required in Multiple Myeloma. Screening and on treatment biopsies are not required in brain tumors and DLBCL patients during dose escalation of intermittent schedules
  7. No prior Avastin Therapy for GBM patients.
  8. Specific tumor types:

    • Non-Hodgkin lymphoma:
    • Diffuse large B-cell lymphoma
    • Primary Brain Tumors: Primary glioblastoma multiforme or gliosarcoma,
    • Hepatocellular Carcinoma
    • Multiple Myeloma

Exclusion Criteria:

  1. Symptomatic central nervous system metastases (excluding GBM). Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
  2. Known symptomatic acute or chronic pancreatitis.
  3. Any peripheral neuropathy ≥ NCI CTCAE grade 2.
  4. Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 2, despite medical management.
  5. Impaired cardiac function or clinically significant cardiac diseases
  6. Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol.
  7. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy.
  8. Major surgery ≤ 2 weeks prior to starting study drug or still recovering from post operative side effects.
  9. Women who are pregnant or breast feeding. Adults of reproductive potential not employing two forms of birth control.
  10. Known HIV infection.
  11. Known chronic hepatitis B or C virus (HBV/HCV) infection, unless comorbidity in subjects with HCC.
  12. Status post solid organ transplant.
  13. Less than 100 days for subjects receiving autologous hematologic stem cell transplant (HSCT); or 6 months for subjects receiving allogenic HSCT or either transplant type, if otherwise not fully recovered from HSCT related toxicity.
  14. Most concurrent second malignancies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421524

Contacts
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
The Regents of the University of California Recruiting
San Francisco, California, United States, 94143
United States, Michigan
The Regents of the University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
United States, New Jersey
The Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
United States, Tennessee
Greenville Hospital System Recruiting
Nashville, Tennessee, United States, 37212
Sarah Cannon Research Institute Tennessee Oncology Drug Development Unit Recruiting
Nashville, Tennessee, United States, 37205
Contact: SRCI Referral Line    615-339-4214      
United States, Texas
Texas Oncology Recruiting
Dallas, Texas, United States, 75246
South Texas Accelerated Research Therapeutics, LLC (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265    Isabel.jimenez@start.stoh.com   
Contact: Rebecca R Arcos, MS    210-593-5284    Rebecca.arcos@start.stoh.com   
Principal Investigator: Drew Rasco, M.D.         
United States, Washington
North Star Lodge Cancer Center Recruiting
Yakima, Washington, United States, 98902
France
CHU Clemenceau Withdrawn
Clichy, Paris, France, 92110
Institut Gustave Roussy Recruiting
Villejuif, Paris, France, 94805
IPC Recruiting
Marseille, France, 13009
Insitut Universitaire du Cancer IUCT - Oncopole Recruiting
Toulouse Cedrex, France, 31059
Italy
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fo Recruiting
Napoli, Campania, Italy, 80131
Istituto di Ematologia e Oncologia Medica - L.A. Seragnoli A.O. Policlinico S.Orsola Malpighi Recruiting
Bologna, Italy, 40138
Instituto Nazionale Tumori-via Venezian Recruiting
Milan, Italy, 20133
Instituto clinic Humanitas Recruiting
Rozzano, Italy, 20089
Spain
Hospital del Mar Recruiting
Barcelona, Spain, 8003
Hospital Universitari Germans Trias i Pujol ICO Recruiting
Barcelona, Spain, 08916
Hospital Universitari Vall Hebrón Recruiting
Barcelona, Spain, 08035
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Hospital Universitario Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
Clinica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Hospital Universitario Clinco de Valencia Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01421524     History of Changes
Other Study ID Numbers: CC-122-ST-001
Study First Received: August 19, 2011
Last Updated: April 13, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Celgene Corporation:
Neoplasm
Malignancy
Carcinoma
Lymphoma
Multiple Myeloma
Pleiotropic Pathway Modifier
DNA-PK inhibitor
Advanced Solid Tumors
Glioblastoma multiforme
Hepatocellular Carcinoma
Diffuse large B-cell lymphoma
Mantel Cell Lymphoma
Advanced unresectable Solid Tumors

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Glioblastoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Oligodendroglioma
Adenocarcinoma
Astrocytoma
Blood Protein Disorders
Carcinoma
Cardiovascular Diseases
Digestive System Diseases
Digestive System Neoplasms
Glioma
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Liver Diseases
Liver Neoplasms
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site

ClinicalTrials.gov processed this record on June 29, 2015