Clinical trial NCT02773030: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed
Refractory
Pharmacokinetics
Safety
Efficacy
CC-220
Relapsed and refractory multiple myeloma
Dexamethasone
Daratumumab
Bortezomib
Newly diagnosed multiple myeloma
Newly diagnosed multiple myeloma transplant non-eligible
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2016-05-16
Enrollment: 466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment
timeFrame: Approximately 3 years
measure: Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment
timeFrame: Approximately 3 years
measure: Overall response rate (ORR) of CC-220 in combination with Dexamethasone (DEX) in Cohort D
timeFrame: Approximately 5 years
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Approximately 5 years
measure: Overall response rate (ORR)
timeFrame: Approximately 5 years
measure: Time to Response (TTR)
timeFrame: Approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Approximately 5 years
measure: Progression-free Survival (PFS)
timeFrame: Approximately 5 years
measure: Overall Survival (OS) in Part 2 relapsed and refractory multiple myeloma (RRMM) cohorts
timeFrame: Approximately 5 years
measure: Pharmacokinetics - Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC[TAU])
timeFrame: Approximately 1 year
measure: Pharmacokinetics - Maximum plasma concentration of drug (Cmax)
timeFrame: Approximately 1 year
measure: Pharmacokinetics - Time to maximum plasma concentration of drug (Tmax)
timeFrame: Approximately 1 year
measure: Very good partial response or better rate (VGPR)
timeFrame: Approximately 4 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Local Institution - 102
state: Arizona
city: Little Rock
country: United States
facility: Local Institution - 107
state: Arkansas
city: Atlanta
country: United States
facility: Local Institution - 101
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 120
state: Illinois
city: Fairway
country: United States
facility: Local Institution - 113
state: Kansas
city: Baltimore
country: United States
facility: Local Institution - 106
state: Maryland
city: Boston
country: United States
facility: Local Institution - 114
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 115
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 110
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 104
state: Michigan
city: Detroit
country: United States
facility: Local Institution - 103
state: Michigan
city: Grand Island
country: United States
facility: Local Institution - 140
state: Nebraska
city: Grand Island
country: United States
facility: Local Institution - 141
state: Nebraska
city: Omaha
country: United States
facility: Local Institution - 137
state: Nebraska
city: Omaha
country: United States
facility: Local Institution - 138
state: Nebraska
city: Omaha
country: United States
facility: Local Institution - 131
state: Nebraska
city: Papillion
country: United States
facility: Local Institution - 139
state: Nebraska
city: Cherry Hill
country: United States
facility: Local Institution - 756
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 108
state: New Jersey
city: Mineola
country: United States
facility: Local Institution - 122
state: New York
city: New York
country: United States
facility: Local Institution - 121
state: New York
city: New York
country: United States
facility: Local Institution - 109
state: New York
city: New York
country: United States
facility: Local Institution - 111
state: New York
city: Rochester
country: United States
facility: Local Institution - 125
state: New York
city: Charlotte
country: United States
facility: Local Institution - 112
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 117
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 124
state: Ohio
city: Philadelphia
country: United States
facility: Local Institution - 116
state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution - 123
state: South Carolina
city: Memphis
country: United States
facility: Local Institution - 134
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 118
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 119
state: Utah
city: Seattle
country: United States
facility: Local Institution - 126
state: Washington
city: Tacoma
country: United States
facility: Local Institution - 132
state: Washington
city: Adelaide
country: Australia
facility: Local Institution - 854
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution - 852
state: Victoria
city: Calgary
country: Canada
facility: Local Institution - 904
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 901
state: British Columbia
city: Halifax
country: Canada
facility: Local Institution - 902
state: Nova Scotia
city: Montreal
country: Canada
facility: Local Institution - 903
state: Quebec
city: Lile Cedax
country: France
facility: Local Institution - 704
city: Pessac
country: France
facility: Local Institution - 701
city: Pierre Benite cedex
country: France
facility: Local Institution - 703
city: Poitiers Cedex
country: France
facility: Local Institution - 702
city: Dresden
country: Germany
facility: Local Institution - 605
city: Dusseldorf
country: Germany
facility: Local Institution - 603
city: Hamburg
country: Germany
facility: Local Institution - 604
city: Heidelberg
country: Germany
facility: Local Institution - 602
city: Tuebingen
country: Germany
facility: Local Institution - 601
city: Wuerzburg
country: Germany
facility: Local Institution - 606
city: Jerusalem
country: Israel
facility: Local Institution - 751
state: Yerushalayim
city: Tel Hashomer
country: Israel
facility: Local Institution - 754
city: Tel-Aviv
country: Israel
facility: Local Institution - 755
city: Meldola
country: Italy
facility: Local Institution - 307
city: Pavia
country: Italy
facility: Local Institution - 305
city: Reggio Emilia
country: Italy
facility: Local Institution - 302
city: Rome
country: Italy
facility: Local Institution - 303
city: Torino
country: Italy
facility: Local Institution - 301
city: Matsuyama
country: Japan
facility: Local Institution - 808
state: Ehime
city: Aomori
country: Japan
facility: Local Institution - 805
city: Hiroshima City
country: Japan
facility: Local Institution - 813
city: Isehara City, Kanagawa
country: Japan
facility: Local Institution - 812
city: Kamogawa
country: Japan
facility: Local Institution - 809
city: Kyoto-city
country: Japan
facility: Local Institution - 802
city: Nagasaki-shi
country: Japan
facility: Local Institution - 811
city: Nagoya
country: Japan
facility: Local Institution - 810
city: Nagoya
country: Japan
facility: Local Institution - 801
city: Ogaki
country: Japan
facility: Local Institution - 815
city: Osaka
country: Japan
facility: Local Institution - 804
city: Sendai
country: Japan
facility: Local Institution - 803
city: Shinagawa-ku, Tokyo
country: Japan
facility: Local Institution - 806
city: Sunto-gun
country: Japan
facility: Local Institution - 814
city: Toyohashi
country: Japan
facility: Local Institution - 807
city: Amsterdam
country: Netherlands
facility: Local Institution - 503
state: NH
city: Maastrich
country: Netherlands
facility: Local Institution - 504
city: Rotterdam
country: Netherlands
facility: Local Institution - 501
city: Utrecht
country: Netherlands
facility: Local Institution - 502
city: Badalona (Barcelona)
country: Spain
facility: Local Institution - 404
city: Barcelona
country: Spain
facility: Local Institution - 401
city: Barcelona
country: Spain
facility: Local Institution - 405
city: Madrid
country: Spain
facility: Local Institution - 408
city: Madrid
country: Spain
facility: Local Institution - 407
city: Pamplona
country: Spain
facility: Local Institution - 402
city: Valencia
country: Spain
facility: Local Institution - 406
city: Birmingham
country: United Kingdom
facility: Local Institution - 205
city: Leeds
country: United Kingdom
facility: Local Institution - 202
city: Oxford
country: United Kingdom
facility: Local Institution - 204
city: Sutton
country: United Kingdom
facility: Local Institution - 201
city: Sutton
country: United Kingdom
facility: Local Institution - 203
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Lonial S, Popat R, Hulin C, Jagannath S, Oriol A, Richardson PG, Facon T, Weisel K, Larsen JT, Minnema MC, Abdallah AO, Badros AZ, Knop S, Stadtmauer EA, Cheng Y, Amatangelo M, Chen M, Nguyen TV, Amin A, Peluso T, van de Donk NWCJ. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022 Nov;9(11):e822-e832. doi: 10.1016/S2352-3026(22)00290-3. Epub 2022 Oct 6.