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

NCT01421524 | Completed Phase 1 DMC

• 2 other identifiers: CC-122-ST-001U1111-1203-5132
• Study Type: interventional
• Target: 271
• Locations: 5 countries
• Sites: 39

Brief Summary

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.

Conditions

Multiple Myeloma; Lymphoma, Large B-Cell, Diffuse; Pleiotropic Pathway Modifier; Glioblastoma; Lymphoma; Primary Central Nervous System Lymphoma

Keywords

Neoplasm; Malignancy; Carcinoma; Lymphoma; Multiple Myeloma; DNA-PK inhibitor; Advanced Solid Tumors; Glioblastoma multiforme; Hepatocellular Carcinoma; Diffuse large B-cell lymphoma; Mantel Cell Lymphoma; Advanced unresectable Solid Tumors; Primary CNS Lymphoma

Outcome Measures

Primary Outcomes (9)

• 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.

  Up to approximately Day 28

• Pharmacokinetics- Cmax

  Maximum observed concentration in plasma (Cmax)

  Up to day 22

• Pharmacokinetics- AUC

  Area under the concentration-time curve

  Up to day 22

• Pharmacokinetics- tmax

  Time to maximum concentration

  Up to day 22

• Pharmacokinetics- t1/2

  Terminal half-life

  Up to day 22

• Pharmacokinetics- CL/F

  Apparent total body clearance

  Up to day 22

• Pharmacokinetics- Vz/F

  Apparent volume of distribution

  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.

  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.

  Up to day 28

Secondary Outcomes (3)

• Response Rate

  up to approximately 6 months

• Tissue concentration of CC-122

  up to approximately 6 months

• 6-month progression free survival (PFS) rate for GBM chort

  Up to approximately 6 months

Study Arms (4)

CC-122 MM-2

EXPERIMENTAL

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

Drug: CC-122

CC-122- DLBCL-2

EXPERIMENTAL

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

CC-122- GBM-2

EXPERIMENTAL

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

Primary Central Nervous System Lymphoma (PCNSL)

EXPERIMENTAL

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

Drug: CC-122

Interventions

CC-122 DRUG

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).

CC-122 MM-2

Eligibility Criteria

• Age: 18 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.
• Men and women, 18 years or older, with histologically or cytologically-confirmed, advanced solid tumors, Non-Hodgkin Lymphona (NHL), Multiple Myloma (MM), or advanced unresectable solid tumors limited to the tumor types below.
• Subjects who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no standard anticancer therapy exists. Must have disease that is objectively measurable
• Measurable disease criteria:
• Subjects with Glioblastoma multiforme (GBM) do not have to have objectively measurable disease at entry.
• For MM, Diffuse large B-cell lymphoma (DLBCL): Subjects must have disease that is objectively measurable, measurable levels of myeloma paraprotein in serum (\> 0.5 g/dL) or urine (\> 0.2 g excreted in a 24-hour collection sample) for MM and measurable disease by Internatonal Working Group (IWG) for NHL (with at least one measurable lesion's longest diameter ≥ 2cm).
• For Primary Central Nervous System (CNS) Lymphoma (PCNSL): Subjects must have disease that is objectively measurable by International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma, Cerebrospinal Fluid (CSF) cytology (in case of leptomeningeal only disease), or vitreal aspiration cytology and/or retinal photographs (in case of ocular lymphoma).
• DLBCL-2 cohort:
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
• Histologically proven diffuse large B-cell non-Hodgkin's lymphoma
• Must have progressed following or have been unable to tolerate at least one prior anthracycline or alkylating agent containing regimen (with or without anti-CD20).
• Platelets ≥ 60 x 109/L.
• For PCNSL cohort:
• ECOG Performance Status of ≤ 2
• Recurrent/refractory CNS non-Hodgkin's lymphoma involving CNS (Brain, Cerebrospinal fluid (CSF) or intraocular compartments)

You may not qualify if:

• History of other carcinomas within the last 5 years except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with a current Prostate-specific antigen (PSA) of \<1.0 mg/dL on 2 evaluations at least 3 months apart; the most recent evaluation must be no more than 4 weeks prior to Day 1 of the study drug, or other malignancies that were completely resected or treated Stage 1/2 lesions currently in complete remission.
• Symptomatic central nervous system metastases (excluding Glioblastoma multiforrme (GBM) and Primary Central Nervous System Lymphoma (PCNSL). Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed.
• Known symptomatic acute or chronic pancreatitis.
• Any peripheral neuropathy ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 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 multigated acquisition (MUGA) scan or echocardiography (ECHO).
• Complete left bundle branch, or bifasicular block.
• Congenital long QT syndrome.
• Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation.
• QTcF \> 460 msec on screening Electrocardiography (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 BNP \>300 pg/mL.
• ° Subjects with baseline troponin-T \>Upper Limit of Normal (ULN) or B-type Natriuretic Peptide (BNP) \>100 pg/mL are eligible but must have cardiologist evaluation prior to enrollment in the trial for baseline assessment 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).

Sponsors & Collaborators

• Celgene: lead

Study Sites (39)

City of Hope Cancer Center

Duarte, California, 91010-300, United States

Location

UCLA Neuro-Oncology Program

Los Angeles, California, 90095, United States

Location

UCSF Helen Diller Medical Center at Parnassus Heights

San Francisco, California, 94143-1270, United States

Location

University Of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Medical Center - New Center One

Detroit, Michigan, 48202-268, United States

Location

Comprehensive Cancer Centers Of Nevada

Las Vegas, Nevada, 89169, United States

Location

Rutgers Cancer Institute of New Jersey University

New Brunswick, New Jersey, 08901, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Local Institution - 020

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MUSC Rheumatology and Immunology Dept.

Charleston, South Carolina, 29425, United States

Location

Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon Research Institute Drug Development Unit

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, PA - Dallas 75246

Dallas, Texas, 75246, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Swedish Medical Center Cancer Institute Research

Seattle, Washington, 98104, United States

Location

Yakima Valley Memorial Hospital/ North Star Lodge

Yakima, Washington, 98902, United States

Location

Local Institution - 401

Brussels, 1200, Belgium

Location

Local Institution - 400

Leuven, 3000, Belgium

Location

Local Institution - 202

Caen, 14033, France

Location

Local Institution - 201

Marseille Le Cedex, 13273, France

Location

Local Institution - 205

Pierre-Bénite, 69495, France

Location

Local Institution - 203

Toulouse, 31059, France

Location

Local Institution - 200

Villejuif, 94805, France

Location

Local Institution - 303

Bologna, 40138, Italy

Location

Local Institution - 305

Bologna, 40139, Italy

Location

Local Institution - 300

Milan, 0, Italy

Location

Local Institution - 302

Napoli, Campania, 80131, Italy

Location

Local Institution - 304

Roma, 00144, Italy

Location

Local Institution - 301

Rozzano (MI), 20089, Italy

Location

Local Institution - 103

Badalona (Barcelona), 8916, Spain

Location

Local Institution - 105

Barcelona, 08003, Spain

Location

Local Institution - 101

Barcelona, 08035, Spain

Location

Local Institution - 104

Madrid, 28040, Spain

Location

Local Institution - 102

Madrid, 28041, Spain

Location

Local Institution - 106

Pamplona, 31008, Spain

Location

Local Institution - 108

Salamanca, 37007, Spain

Location

Local Institution - 107

Seville, 41013, Spain

Location

Local Institution - 100

Valencia, 46010, Spain

Location

Related Publications (4)

• Rasco DW, Papadopoulos KP, Pourdehnad M, Gandhi AK, Hagner PR, Li Y, Wei X, Chopra R, Hege K, DiMartino J, Shih K. A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies. Clin Cancer Res. 2019 Jan 1;25(1):90-98. doi: 10.1158/1078-0432.CCR-18-1203. Epub 2018 Sep 10.

  PMID: 30201761 BACKGROUND

• Cubillos-Zapata C, Cordoba R, Avendano-Ortiz J, Arribas-Jimenez C, Hernandez-Jimenez E, Toledano V, Villaescusa T, Moreno V, Lopez-Collazo E. CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma. Oncoimmunology. 2016 Sep 16;5(12):e1231290. doi: 10.1080/2162402X.2016.1231290. eCollection 2016.

  PMID: 28255524 BACKGROUND

• Hagner P, et al. CC-122 Has Potent Anti-Lymphoma Activity through Destruction of the Aiolos and Ikaros Transcription Factors and Induction of Interferon Response Pathways. Presented at American Society of Hematology 2014, December 6-9, 2014, San Francisco, CA. Abstract No. 3035.

  BACKGROUND

• Carpio C, Bouabdallah R, Ysebaert L, Sancho JM, Salles G, Cordoba R, Pinto A, Gharibo M, Rasco D, Panizo C, Lopez-Martin JA, Santoro A, Salar A, Damian S, Martin A, Verhoef G, Van den Neste E, Wang M, Couto S, Carrancio S, Weng A, Wang X, Schmitz F, Wei X, Hege K, Trotter MWB, Risueno A, Buchholz TJ, Hagner PR, Gandhi AK, Pourdehnad M, Ribrag V. Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a predictive gene classifier. Blood. 2020 Mar 26;135(13):996-1007. doi: 10.1182/blood.2019002395.

  PMID: 31977002 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Large B-Cell, Diffuse; Glioblastoma; Lymphoma; Neoplasms; Carcinoma; Carcinoma, Hepatocellular

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphatic Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 19, 2011
• First Posted: August 23, 2011
• Study Start: September 12, 2011
• Primary Completion: November 21, 2023
• Study Completion: November 21, 2023
• Last Updated: December 12, 2023

Record last verified: 2023-11

Locations

IT (6); FR (5); US (17); BE (2); ES (9)