RELAPSED AND REFRACTORY MULTIPLE MYELOMA MedDRA version: 21.1 Level: LLT Classification code 10067095 Term: Multiple myeloma progression System Organ Class: 100000004864 MedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: CC-220
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-220
CAS Number: 1560678-63-8
Current Sponsor code: CC-220
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria: 1. Subject is =18 years of age at the time of signing the ICF. 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements 4. Subjects must have a documented diagnosis of MM and have measurable disease as further defined in the protocol. 5. Subjects in Cohorts A, B, C, and E must have received at least 2 prior myeloma regimens (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen). Subjects in Cohort F must have received at least 1 prior myeloma regimen. Subjects in Cohort D must have received at least 3 prior myeloma regimens. 6. All subjects must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen. Subjects in Cohort D must have received prior treatment with at least 2 consecutive cycles of a lenalidomide-containing regimen and at least 2 consecutive cycles of a pomalidomide-containing regimen. 7. All subjects must have received prior treatment with at least 2 consecutive cycles of a proteasome inhibitor or a proteasome inhibitor-containing regimen 8. For Part 2 (Cohort C and Cohort D), all subjects must have received prior treatment with at least 2 consecutive cycles of a CD38 antibody or a CD38 antibody-containing regimen 9. All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy. Subjects who had CAR T therapy as their last myeloma therapy must have documented disease progression. 10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 11. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must: a) Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact. b) Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of CC220, 90 days after the last dose of DARA (Cohort E) or 7 months after the last dose of BTZ (Cohort F), whichever is longer. Contraception requirements are detailed in the Protocol Appendix D. 12. Male subjects must: a. Practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following the las
Exclusion criteria
Exclusion criteria: 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 3. Subject has any condition that confounds the ability to interpret data from the study 4. Subject has nonsecretory or oligosecretory multiple myeloma 5. Subjects with Plasma Cell leukemia or amyloidosis 6. Any of the following laboratory abnormalities ·Absolute neutrophil count (ANC) 13.5 mg/dL (> 3.4 mmol/L) ·Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) =2.0 x upper limit of normal (ULN) ·Serum total bilirubin and alkaline phosphatase >1.5 x ULN ·Subjects with serious renal impairment (creatinine clearance [CrCl] <45 mL/min) or requiring dialysis would be excluded 7. Subjects with peripheral neuropathy =Grade 2 8. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220 9. Subjects with a prior history of malignancies, other than MM, unless the subject has been free of the disease for =5 years with the exception of the following noninvasive malignancies: ·Basal cell carcinoma of the skin ·Squamous cell carcinoma of the skin ·Carcinoma in situ of the cervix ·Carcinoma in situ of the breast ·Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative 10. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, DEX, daratumumab (for Cohort E), bortezomib (for Cohort F). Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-220, DEX, daratumumab (for Cohort E), bortezomib (for Cohort F). 11. Contraindications to the other treatment regimens, as per local prescribing information. 12. Subject has received any of the following within the last 14 days of initiating IP: ·Plasmapheresis ·Major surgery (as defined by the Investigator) ·Radiation therapy other than local therapy for MM associated bone lesions ·Use of any systemic myeloma drug therapy 13, Subject has been treated with an investigational agent (ie, an agent not commercially available) within 28 days or 5 half-lives (whichever is longer) of initiating IP. Not applicable for subjects who had CAR T as last prior regimen. 14. Subject has any one of the following: ·Clinically significant abnormal electrocardiogram (ECG) finding at Screening ·Congestive heart failure ·Myocardial infarction within 12 months prior to starting IP ·Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris 15. Subject has current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions to this criterion: ·Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection) ·Systemic corticosteroids at physiologic dos
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study include: Part 1 To determine the maximum tolerated doses (MTDs) and/or recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy (MonoT), in combination with dexamethasone (DEX) (DoubleT), in combination with dexamethasone and daratumumab (CC-220Dd), and in combination with DEX and bortezomib (CC-220Vd) in subjects with relapsed and refractory multiple myeloma (RRMM). Part 2 To determine the efficacy of CC-220 in combination with DEX (Double T) in subjects with RRMM in Cohort D, as measured by overall response rate (ORR).;Secondary Objective: - To evaluate the safety of CC-220 as MonoT, DoubleT, CC-220Dd, and CC-220Vd in subjects with RRMM. - To evaluate additional efficacy parameters of CC-220 in combination with DEX including time-to-response (TTR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in subjects with RRMM in Cohort D. - To assess the preliminary efficacy of CC-220 as MonoT, DoubleT, CC-220Dd, and CC-220Vd in subjects with RRMM in Part 1. - To evaluate the pharmacokinetics (PK) of CC-220 in subjects with RRMM ;Primary end point(s): Recommended Dose and regimen in Part 1 - Establish the maximum tolerated doses (MTDs) and/or Recommended Phase 2 doses (RP2Ds) of CC-220 monotherapy, in combination with DEX, and in combination with DEX and daratumumab (CC-220Dd), and in combination with DEX and bortezomib (CC-220Vd). Overall response rate (ORR) in Cohort D- Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) in CC-220 in combination with DEX ;Timepoint(s) of evaluation of this end point: The endpoint of Recommended Dose and Regimen in Part 1- Part 1 Overall response rate (ORR) in Cohort D- From first subject first dose of IP until the last subject is no longer evaluable for response or has progressed. Further details are available in the clinical study prot | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Safety - Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product -Overall Response Rate (ORR) - Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar 2016) for subjects who achieved partial response (PR) or better -Time to Response (TTR) - Time from enrollment to response (PR or greater) -Duration of Response (DOR) - Time from the first documentation of response (PR or greater) to the first documentation of PD -Progression-free Survival (PFS) - Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first -Overall Survival (OS) in Part 2 RRMM cohorts - Time from first dose of IP to death due to any cause -Pharmacokinetic (PK) parameters - PK of CC-220, and as appropriate, its R-enantiomer CC-17195 in plasma, eg, area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC0-t), maximum plasma concentration of drug (Cmax), time to Cmax (Tmax), terminal-phase elimination half life (t1/2), apparent total plasma clearance when dosed daily (CLss/F) and apparent total volume of distribution at steady state when dosed orally (Vss/F);Timepoint(s) of evaluation of this end point: Safety - From first subject first visit until 28 days after the last subject discontinues study treatment. Overall response rate (ORR) -From first subject dose of IP until the last subject is no longer evaluable for response or has progressed. Time to response (TTR) -From first subject dose of IP until the last subject is no longer evaluable for response or has progressed. Duration of Response (DOR)-From first subject dose of IP until the last subject is no longer evaluable for response or has progressed. Progression-free Survival (PFS)-From first subject first dose of IP unt | — |
Countries
France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed