A Study to Determine Dose and Tolerability of CC-220 Monotherapy, in Combination With Dexamethasone, and in Combination With Dexamethasone and Daratumumab or Bortezomib in Subjects With Relapsed and Refractory Multiple Myeloma (MM)
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| ClinicalTrials.gov Identifier: NCT02773030 |
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Recruitment Status :
Recruiting
First Posted : May 16, 2016
Last Update Posted : October 22, 2019
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Sponsor:
Celgene
Information provided by (Responsible Party):
Celgene
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Brief Summary:
This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study consisting of two parts: dose escalation (Part 1) for CC-220 MonoT, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ; and the expansion of the RP2D (Part 2) for CC-220 MonoT and CC-220 in combination with DEX (DoubleT).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: CC-220 Drug: Dexamethasone Drug: Daratumumab Drug: Bortezomib (BTZ) Drug: Carfilzomib | Phase 1 Phase 2 |
Subjects assigned to CC-220 monotherapy, who develop progressive disease (PD) will have the option to receive DEX in addition to CC-220 after consultation with the Medical Monitor. The dose of CC-220 will not be higher than the dose of CC-220 used in combination with dexamethasone in Cohort B that has been determined to be safe. Progressive disease must be confirmed in accordance with international myeloma working group (IMWG) criteria.
The starting dose of DEX will be 40 mg for subjects who are ≤75 years of age and 20 mg for subjects who are >75 years of age, given once weekly. This treatment will continue until PD, unacceptable toxicity or the subject withdraws consent.
For Cohorts A and B, the starting dose level of CC-220, dose level 1, is 0.3 mg. A dose level -1, of 0.15 mg, may also be evaluated if the starting dose level of 0.3 mg for 21 days of a 28-day cycle is not tolerated. For Cohorts E and F, the starting dose level of CC-220, dose level 1, is one dose level below the maximum dose for Cohort B that has been determined to be safe by the dose escalation committee (DEC) at the start of enrollment for both cohorts. For Cohort E in addition to CC-220 and DEX, daratumumab will be administered intravenously (IV) at a 16mg/kg dose. For Cohort F in addition to CC-220 and DEX, bortezomib will be administered subcutaneous (SC) at a 1.3mg/m2 dose.
All subjects with a minimal response (MR) or better who discontinue study treatment in Part 1 or Part 2 of the study for a reason other than PD or withdrawal of consent from the study will be followed for response assessment every 28 days (every 21 days for Cohort F) until PD.
The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.
The initiation of Part 2 will begin when the RP2D is established in Part 1 in either Cohort A or Cohort B. Either cohort may begin once the RP2D is determined for each cohort independently during Part 1. All expansion decisions will be determined by the DEC after review of all safety, PK, biomarker and preliminary efficacy data, as applicable. During Part 2, the Independent Expert Reviewer will review safety data and any other data deemed relevant so that subject safety is ensured.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 303 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b/2a Multicenter, Open-label, Dose-escalation Study to Determine the Maximum Tolerated Dose, Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CC-220 Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma |
| Actual Study Start Date : | October 14, 2016 |
| Estimated Primary Completion Date : | April 16, 2021 |
| Estimated Study Completion Date : | February 14, 2026 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A: CC-220 Monotherapy - Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide |
Experimental: Cohort B: CC-220 in combination with Dexamethasone - Part 1
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron |
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Experimental: Cohort C: CC-220 Monotherapy - Part 2
Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide |
Experimental: Cohort D: CC-220 in combination with Dexamethasone - Part 2
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron |
Experimental: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron Drug: Daratumumab Daratumumab (DARA) 16mg/kg by intravenous infusion on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.
Other Name: Darzalex |
Experimental: Cohort F: CC-220 with DEX and bortezomib - Part 1
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron Drug: Bortezomib (BTZ) Bortezomib 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.
Other Name: Velcade |
Experimental: Cohort G1 - CC-220 in combination with once weekly CFZ and DEX
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron Drug: Carfilzomib Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.
Other Name: Kyprolis |
Experimental: Cohort G2 -CC-220 in combination with twice weekly CFZ and DEX
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Drug: CC-220
CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Other Name: Iberdomide Drug: Dexamethasone Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Other Name: Decadron Drug: Carfilzomib Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.
Other Name: Kyprolis |
Primary Outcome Measures :
- Maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 1 year ]Establish the maximum tolerated doses (MTDs) of CC-220 monotherapy, in combination with DEX, and in combination with DEX and daratumumab (CC-220Dd), in combination with DEX and bortezomib (CC-220Vd), and in combination with DEX and carfilzomib (CC-220Kd)
- Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 1 year ]RP2D is defined as the dose selected for phase 2 based on safety, pharmacokinetics and biomarker data from phase 1 of the study.
- Overall response rate (ORR) of CC-220 in combination with DEX in Part 2 [ Time Frame: Approximately 3 years ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Rajkumar, 2011) in CC-220 in combination with DEX
Secondary Outcome Measures :
- Adverse Events (AEs) [ Time Frame: Approximately 3 years ]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) [ Time Frame: Approximately 3 years ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Rajkumar, 2011)
- Time to Response (TTR) [ Time Frame: Approximately 3 years ]Is defined as the time from the first date of dosing of IP to the first date of documented response (partial response [PR] or greater).
- Duration of Response (DOR) [ Time Frame: Approximately 3 years ]Is defined as Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)
- Pharmacokinetics ‐AUC 0-τ [ Time Frame: Approximately 1 year ]Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval
- Pharmacokinetics ‐Cmax [ Time Frame: Approximately 1 year ]Maximum plasma concentration of drug
- Pharmacokinetics ‐Tmax [ Time Frame: Approximately 1 year ]Time to Maximum plasma concentration of drug
- Pharmacokinetics ‐t1/2 [ Time Frame: Approximately 1 year ]Terminal-phase elimination half life
- Pharmacokinetics ‐CLss/F [ Time Frame: Approximately 1 year ]Apparent total plasma clearance when dosed daily
- Pharmacokinetics ‐Vss/F [ Time Frame: Approximately 1 year ]Apparent total volume of distribution at steady state when dosed orally
- Progression-free Survival (PFS) [ Time Frame: Approximately 3 years ]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 [ Time Frame: Approximately 3 years ]Time from first dose of IP to death due to any cause
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Subjects must have a documented diagnosis of Multiple Myeloma and have measurable disease defined as:
- M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours and/or
- Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
- All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
Exclusion Criteria:
- Subject has nonsecretory or oligosecretory multiple myeloma
- Subjects with Plasma Cell leukemia or amyloidosis
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Any of the following laboratory abnormalities
- Absolute neutrophil count (ANC) <1,000/μL
- Platelet count <75,000/μL
- Corrected serum calcium >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 ([CrCl] <50 mL/min) or requiring dialysis would be excluded
- Subjects with peripheral neuropathy ≥Grade 2
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773030
Contacts
| Contact: Associate Director Clinical Trial Disclosure | 1-888-260-1599 | clinicaltrialdisclosure@celgene.com |
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Sponsors and Collaborators
Celgene
Investigators
| Study Director: | Amine Bensmaine, MD | Celgene Corporation |
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT02773030 History of Changes |
| Other Study ID Numbers: |
CC-220-MM-001 U1111-1182-9200 ( Registry Identifier: WHO ) 2016-000860-40 ( EudraCT Number ) |
| First Posted: | May 16, 2016 Key Record Dates |
| Last Update Posted: | October 22, 2019 |
| Last Verified: | October 2019 |
Keywords provided by Celgene:
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Multiple Myeloma Relapsed Refractory Pharmacokinetics Safety Efficacy |
CC-220 Relapsed and refractory multiple myeloma Dexamethasone Daratumumab Bortezomib |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Dexamethasone acetate Bortezomib Daratumumab BB 1101 Antibodies, Monoclonal Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal |