A Study to Determine Dose, Safety, Tolerability, Drug Levels, and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Participants With Multiple Myeloma

Multiple Myeloma Clinical Trial

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 as Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02773030
• Other study ID #: CC-220-MM-001
• Secondary ID: U1111-1182-92002
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 14, 2016
• Est. completion date: February 6, 2028

Study information

• Verified date: April 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 monotherapy, 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 monotherapy and CC-220 in combination with DEX for Relapsed Refractory Multiple Myeloma (RRMM), CC-220 in combination with DEX and BTZ, and CC-220 in combination with DEX and DARA for Newly Diagnosed Multiple Myeloma (NDMM).

Description:

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.

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 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 recommended phase 2 dose (RP2D) is established in Part 1 in either Cohort A, Cohort B, Cohort E or Cohort F. The cohorts 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 532
• Est. completion date: February 6, 2028
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2

• Relapsed and refractory multiple myeloma (RRMM) participants must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy

• Newly diagnosed multiple myeloma (NDMM) participants must have documented diagnosis with previously untreated symptomatic multiple myeloma (MM)

• Participants in Cohorts J1 and K are those for whom autologous stem cell transplantation is not planned for initial therapy or are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation

Exclusion Criteria:

• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study

• Nonsecretory multiple myeloma

• Prior history of malignancies, other than MM and select non-invasive malignancies, unless the participant has been free of the disease for = 5 years

Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• CC-220
Specified dose on specified days
• Dexamethasone
Specified dose on specified days
• Daratumumab
Specified dose on specified days
• Bortezomib
Specified dose on specified days
• Carfilzomib
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution - 854	Adelaide	South Australia
Australia	Local Institution - 852	Box Hill	Victoria
Canada	Local Institution - 904	Calgary	Alberta
Canada	Local Institution - 902	Halifax	Nova Scotia
Canada	Local Institution - 903	Montreal	Quebec
Canada	Local Institution - 901	Vancouver	British Columbia
France	Local Institution - 704	Lile Cedax
France	Local Institution - 701	Pessac
France	Local Institution - 703	Pierre Benite cedex
France	Local Institution - 702	Poitiers Cedex
Germany	Local Institution - 605	Dresden
Germany	Local Institution - 603	Dusseldorf
Germany	Local Institution - 604	Hamburg
Germany	Local Institution - 602	Heidelberg
Germany	Local Institution - 601	Tuebingen
Germany	Local Institution - 606	Wuerzburg
Israel	Local Institution - 751	Jerusalem	Yerushalayim
Israel	Local Institution - 754	Tel Hashomer
Israel	Local Institution - 755	Tel-Aviv
Italy	Local Institution - 307	Meldola
Italy	Local Institution - 305	Pavia
Italy	Local Institution - 302	Reggio Emilia
Italy	Local Institution - 303	Rome
Italy	Local Institution - 301	Torino
Japan	Local Institution - 805	Aomori
Japan	Local Institution - 813	Hiroshima City
Japan	Local Institution - 812	Isehara City, Kanagawa
Japan	Local Institution - 809	Kamogawa
Japan	Local Institution - 802	Kyoto-city
Japan	Local Institution - 808	Matsuyama	Ehime
Japan	Local Institution - 811	Nagasaki-shi
Japan	Local Institution - 801	Nagoya
Japan	Local Institution - 810	Nagoya
Japan	Local Institution - 815	Ogaki
Japan	Local Institution - 804	Osaka
Japan	Local Institution - 803	Sendai
Japan	Local Institution - 806	Shinagawa-ku, Tokyo
Japan	Local Institution - 814	Sunto-gun
Japan	Local Institution - 807	Toyohashi
Netherlands	Local Institution - 503	Amsterdam
Netherlands	Local Institution - 504	Maastrich
Netherlands	Local Institution - 501	Rotterdam
Netherlands	Local Institution - 502	Utrecht
Spain	Local Institution - 404	Badalona (Barcelona)
Spain	Local Institution - 401	Barcelona
Spain	Local Institution - 405	Barcelona
Spain	Local Institution - 407	Madrid
Spain	Local Institution - 408	Madrid
Spain	Local Institution - 402	Pamplona
Spain	Local Institution - 406	Valencia
United Kingdom	Local Institution - 205	Birmingham
United Kingdom	Local Institution - 202	Leeds
United Kingdom	Local Institution - 204	Oxford
United Kingdom	Local Institution - 201	Sutton
United Kingdom	Local Institution - 203	Sutton
United States	Local Institution - 104	Ann Arbor	Michigan
United States	Local Institution - 101	Atlanta	Georgia
United States	Local Institution - 106	Baltimore	Maryland
United States	Local Institution - 110	Boston	Massachusetts
United States	Local Institution - 114	Boston	Massachusetts
United States	Local Institution - 115	Boston	Massachusetts
United States	Local Institution - 112	Charlotte	North Carolina
United States	Local Institution - 756	Cherry Hill	New Jersey
United States	Local Institution - 120	Chicago	Illinois
United States	Local Institution - 117	Cleveland	Ohio
United States	Local Institution - 124	Columbus	Ohio
United States	Local Institution - 118	Dallas	Texas
United States	Local Institution - 103	Detroit	Michigan
United States	Local Institution - 113	Fairway	Kansas
United States	Local Institution - 140	Grand Island	Nebraska
United States	Local Institution - 141	Grand Island	Nebraska
United States	Local Institution - 123	Greenville	South Carolina
United States	Local Institution - 108	Hackensack	New Jersey
United States	Local Institution - 107	Little Rock	Arkansas
United States	Local Institution - 134	Memphis	Tennessee
United States	Local Institution - 122	Mineola	New York
United States	Local Institution - 109	New York	New York
United States	Local Institution - 111	New York	New York
United States	Local Institution - 121	New York	New York
United States	Local Institution - 131	Omaha	Nebraska
United States	Local Institution - 137	Omaha	Nebraska
United States	Local Institution - 138	Omaha	Nebraska
United States	Local Institution - 139	Papillion	Nebraska
United States	Local Institution - 116	Philadelphia	Pennsylvania
United States	Local Institution - 125	Rochester	New York
United States	Local Institution - 119	Salt Lake City	Utah
United States	Local Institution - 102	Scottsdale	Arizona
United States	Local Institution - 126	Seattle	Washington
United States	Local Institution - 132	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Israel,  Italy,  Japan,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment	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)	Approximately 3 years
Primary	Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment	RP2D is defined as the dose selected for phase 2 based on safety, pharmacokinetics and biomarker data from phase 1 of the study	Approximately 3 years
Primary	Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort D	Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2011) in CC-220 in combination with DEX	Approximately 5 years
Secondary	Adverse Events (AEs)	Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product	Approximately 5 years
Secondary	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	Approximately 5 years
Secondary	Time to Response (TTR)	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)	Approximately 5 years
Secondary	Duration of Response (DOR)	Is defined as Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)	Approximately 5 years
Secondary	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	Approximately 5 years
Secondary	Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohorts	Time from first dose of IP to death due to any cause	Approximately 5 years
Secondary	Pharmacokinetics - Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC[TAU])		Approximately 1 year
Secondary	Pharmacokinetics - Maximum plasma concentration of drug (Cmax)		Approximately 1 year
Secondary	Pharmacokinetics - Time to maximum plasma concentration of drug (Tmax)		Approximately 1 year
Secondary	Very good partial response or better rate (VGPR)	Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) for subjects who achieved VGPR or better	Approximately 4 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting