Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03374085




Registration number
NCT03374085
Ethics application status
Date submitted
1/12/2017
Date registered
15/12/2017
Date last updated
4/10/2023

Titles & IDs
Public title
A Safety, PK and Efficacy Study of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)
Scientific title
A Phase 1/2 Multicenter, Open-label Study to Assess the Safety, Pharmacokinetics and Efficacy of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
U1111-1205-3650
Secondary ID [2] 0 0
CC-92480-MM-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CC-92480
Treatment: Drugs - Dexamethasone

Experimental: Administration of CC-92480 in combination with dexamethasone - Part 1: Escalating doses of CC-92480 plus a fixed dose of dexamethasone Part 2: RP2D of CC-92480 in combination with dexamethasone

Experimental: Administration of CC-92480 monotherapy - Escalating doses of CC-92480 Monotherapy administered according to different dosing schedules


Treatment: Drugs: CC-92480
CC-92480

Treatment: Drugs: Dexamethasone
Dexamethasone
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events (AEs)
Timepoint [1] 0 0
From enrollment until at least 28 days after completion of study treatment
Primary outcome [2] 0 0
Pharmacokinetics- AUC
Timepoint [2] 0 0
Up to approximately 28 days
Primary outcome [3] 0 0
Pharmacokinetics- Cmax
Timepoint [3] 0 0
Up to approximately 28 days
Primary outcome [4] 0 0
Pharmacokinetics- Tmax
Timepoint [4] 0 0
Up to approximately 28 days
Primary outcome [5] 0 0
Pharmacokinetics- t1/2
Timepoint [5] 0 0
Up to approximately 28 days
Primary outcome [6] 0 0
Pharmacokinetics- CL/F
Timepoint [6] 0 0
Up to approximately 28 days
Primary outcome [7] 0 0
Pharmacokinetics- Vz/F
Timepoint [7] 0 0
Up to approximately 28 days
Primary outcome [8] 0 0
Maximum tolerated dose (MTD)
Timepoint [8] 0 0
Up to approximately 28 days
Primary outcome [9] 0 0
Overall Response Rate (ORR)
Timepoint [9] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Overall response rate (ORR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
Time to response (TTR)
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
Duration of response (DOR)
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
Progression free survival
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
Adverse Events (AEs)
Timepoint [6] 0 0
Time from first dose of CC-92480 to death due to any cause

Eligibility
Key inclusion criteria
1. Subject is = 18 years of age at the time of signing the informed consent form (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. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
5. Subjects must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:

* M-protein quantities = 0.5 g/dL by sPEP or
* = 200 mg/24 hour urine collection by uPEP or
* Serum FLC levels > 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (?/?) ratio in subjects without measurable serum or urine M-protein or
* For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level = 0.50 g/dL.
6. All subjects must have:

* Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and a CD38 antibody (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen).
* 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 are eligible as long as they have documented disease progression following CAR-T therapy.
* In addition to criteria above (a and b), subjects enrolled in Part 2 must have disease refractory to an immunomodulatory agent (lenalidomide and/or pomalidomide), a glucocorticoid, a proteasome inhibitor, and a CD38 antibody. Refractory is defined as disease that is nonresponsive on therapy (failure to achieve minimal response or development of progressive disease), or progresses within 60 days of last dose.
7. Subjects must have the following laboratory values:

* Absolute neutrophil count (ANC) = 1.25 x 109/L without growth factor support for = 7 days (= 14 days for pegfilgrastim). ANC of = 1.00 x 109/L is permitted for the dose expansion cohorts (Part 2).
* Hemoglobin (Hgb) = 8 g/dL.
* Platelets (plt) = 75 x 109/L without transfusion for = 7 days.
* Corrected serum calcium = 13.5 mg/dL (= 3.4 mmol/L).
* Creatinine clearance (CrCl) based on Cockcroft-Gault formula = 45 mL/min.
* AST/SGOT and ALT/SGPT = 3.0 x upper limit of normal (ULN).
* Serum bilirubin = 1.5 x ULN or < 3.0 mg/dL for subjects with documented Gilbert's syndrome.
* Uric acid = 7.5 mg/dL (446 µmol/L).
* PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
8. Females of childbearing potential (FCBP) must:

* Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after discontinuation of CC-92480. This applies even if the subject practices true abstinence* from heterosexual contact.
* 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 reliable forms of contraception as defined in the PPP and provided to the subject at the time of informed consent, without interruption, 28 days prior to starting CC-92480, during the study therapy (including during dose interruptions), and for 184 days after the last dose of CC-92480.

Note: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point and, 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).

1. Male subjects must:

Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use of a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (even during dose interruptions) and for at least 94 days following CC-92480 last dose in accordance with the PPP provided to the subject at the time of informed consent, even if he has undergone a successful vasectomy.

* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and coitus interruptus (withdrawal) are not acceptable methods of contraception.
2. Males must agree to refrain from donating sperm while on CC-92480 for 94 days after the last dose of CC-92480. Females must agree to refrain from donating ova while on CC-92480 for 184 days after last dose.
3. All subjects must agree to refrain from donating blood while on CC-92480 and for 28 days after its discontinuation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has a 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 non-secretory multiple myeloma.
5. Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen).
6. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
7. Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
8. Subject has immunoglobulin class M (IgM) myeloma.
9. Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression.
10. Subject is undergoing dialysis.
11. Subjects with peripheral neuropathy = Grade 2.
12. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480.
13. Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:

* LVEF < 45% as determined by ECHO or MUGA scan at Screening.
* Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiographic (ECG) finding at Screening.
* A prolongation of QT interval on Screening ECG as defined by repeated demonstration of a QTc interval >480 milliseconds (ms) using Fridericia's QT correction formula; a history of or current risk factors for Torsades de Pointe (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome); and concurrent administration of medications that prolong the QT/QTc interval.
* Congestive heart failure (New York Heart Association Class III or IV).
* Myocardial infarction =6 months prior to starting CC-92480.
* Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris.
14. Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) = 2 weeks prior to starting CC-92480.
15. Subject had prior systemic myeloma treatment with an investigational anti-myeloma agent (eg, anti-PD-1, anti-PD-L1) = 5 half-lives prior to starting CC-92480 (not applicable for subjects who had CAR-T as last prior regimen); subject had prior exposure to approved myeloma therapies (including therapeutic monoclonal antibodies such as anti-CD38 or anti-SLAMF7) = 5 half-lives or within 4 weeks prior to starting CC-92480 whichever is shorter.
16. Subject had major surgery = 2 weeks prior to starting CC-92480. Note: Subjects must have recovered from any clinically significant effects of recent surgery.
17. Subject is a pregnant or nursing female, or intends to become pregnant or donate ova during participation in the study.
18. Subject has known human immunodeficiency virus (HIV) infection.
19. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.
20. Subject has a history of concurrent second cancer requiring ongoing systemic treatment.
21. Subjects has a history of prior malignancy other than MM, except if the subject has been free of disease for =3 years OR the subject had one of the following noninvasive malignancies treated with curative intent without known recurrence:

* Basal or squamous cell carcinoma of the skin.
* Carcinoma in situ of the cervix or breast.
* Stage 1 bladder cancer.
* Incidental histological findings of localized prostate cancer such as tumor stage 1a or 1b (T1a or T1b) using the Tumor/Node/Metastasis (TNM) classification of malignant tumors OR prostate cancer that has been treated with curative intent.
22. Subject has a history of anaphylaxis to thalidomide, lenalidomide, pomalidomide or dexamethasone.
23. Subject has known or suspected hypersensitivity to the excipients (excipients include silica dimethyl silylate, anhydrous colloidal silicon dioxide, mannitol, fumaric acid and stearic acid) contained in the formulation of CC-92480 or dexamethasone.
24. Subject has undergone either of the following within 14 days of initiating CC-92480:

* Plasmapheresis.
* Radiation therapy other than local therapy for symptomatic relief of MM associated bone lesions.
25. Subject has received immunosuppressive medication within 14 days prior to the first dose of CC-92480. The following are exceptions to this criterion:

* Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection).
* Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent.
* Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
26. Subject is unable or unwilling to undergo protocol required venous thromboembolism (VTE) prophylaxis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2028
Actual
Sample size
Target
201
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - 804 - Camperdown
Recruitment hospital [2] 0 0
Local Institution - 802 - Adelaide
Recruitment hospital [3] 0 0
Local Institution - 805 - Clayton
Recruitment hospital [4] 0 0
Local Institution - 803 - Melbourne
Recruitment hospital [5] 0 0
Local Institution - 806 - Fitzroy
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
South Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Belgium
State/province [10] 0 0
Antwerpen
Country [11] 0 0
Belgium
State/province [11] 0 0
Gent
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Belgium
State/province [13] 0 0
Yvoir
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Denmark
State/province [17] 0 0
Aarhus N
Country [18] 0 0
Denmark
State/province [18] 0 0
Copenhagen
Country [19] 0 0
Denmark
State/province [19] 0 0
Odense
Country [20] 0 0
Finland
State/province [20] 0 0
Helsinki
Country [21] 0 0
Greece
State/province [21] 0 0
Athens
Country [22] 0 0
Japan
State/province [22] 0 0
Chuo-ku,chiba
Country [23] 0 0
Japan
State/province [23] 0 0
Fukuoka
Country [24] 0 0
Japan
State/province [24] 0 0
Kashiwa
Country [25] 0 0
Japan
State/province [25] 0 0
Kobe-city
Country [26] 0 0
Japan
State/province [26] 0 0
Kyoto-City
Country [27] 0 0
Japan
State/province [27] 0 0
Okayama
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Spain
State/province [29] 0 0
Badalona (Barcelona)
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Caceres
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Spain
State/province [33] 0 0
Pamplona
Country [34] 0 0
Spain
State/province [34] 0 0
Pozuelo de Alarcon
Country [35] 0 0
Spain
State/province [35] 0 0
Salamanca
Country [36] 0 0
Spain
State/province [36] 0 0
Santander
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Devon
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Cardiff
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Newcastle Upon Tyne
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Oxford
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03374085