A study of the efficacy and safety of the combination of pomalidomide-bortezomib-low-dose dexamethasone compared to just the combination of bortezomib-low-dose dexamethasone in subjects with multiple myeloma that have relapsed after treatment or that have not responded to previous therapy

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2014-000268-17-GR
• Date of registration: 26/05/2015
• Prospective Registration: No
• Primary sponsor: Celgene Corporation
• Public title: A study of the efficacy and safety of the combination of pomalidomide-bortezomib-low-dose dexamethasone compared to just the combination of bortezomib-low-dose dexamethasone in subjects with multiple myeloma that have relapsed after treatment or that have not responded to previous therapy
• Scientific title: A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO COMPARE THE EFFICACY AND SAFETY OF POMALIDOMIDE, BORTEZOMIB AND LOW-DOSE DEXAMETHASONE VERSUS BORTEZOMIB AND LOW-DOSE DEXAMETHASONE IN SUBJECTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
• Date of first enrolment: 22/05/2015
• Target sample size: 559
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000268-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1. Must be = 18 years at the time of signing the informed consent form.
2. The subject must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Subjects must have documented diagnosis of multiple myeloma and have measurable disease by serum or urine protein electrophoresis (sPEP or uPEP): sPEP = 0.5 g/dL or uPEP = 200 mg/24 hours.
5. All subjects must have had at least 1 but no greater than 3 prior anti-myeloma regimens. (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen.)
6. All subjects must have documented disease progression during or after their last anti-myeloma therapy.
7. All subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles.
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
9. Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 4 weeks before starting study treatment, while participating in the study treatment phase(including dose interruptions), and for at least 4 weeks after the last dose of POM or 3 months after the last dose of BTZ, whichever is longer, and must agree to regular pregnancy testing during this timeframe.
10. Females must agree to abstain from breastfeeding during study treatment and for at least 4 weeks after study treatment discontinuation.
11. Males must agree to use a latex or synthetic condom during any sexual contact with FCBP while participating in the study treatment phase and for at least 4 weeks after the last dose of POM or 3 month after the last dose of BTZ, whichever is longer, even if he has undergone a successful vasectomy.
12. Males must also agree to refrain from donating sperm while on pomalidomide and for 4 weeks after discontinuation from this study treatment.
13. All subjects must agree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.
14. All subjects must agree not to share medication.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 232
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 327

Exclusion criteria:
1. Subjects who had documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m2 dose twice weekly dosing schedule
2. Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization
3. Non-secretory multiple myeloma
4. Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) < 1,000/µL
• Hemoglobin < 8 g/dL (< 4.9 mmol/L)
• Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/ µL for subjects in whom = 50% of bone marrow nucleated cells are plasma cells
• Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
• Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
• Serum total bilirubin > 1.5 x ULN
5. Subjects with severe renal impairment (Creatinine Clearance [CrCl] <30 mL/min) requiring dialysis
6. Subjects with 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 non-invasive 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 histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
7. Previous therapy with pomalidomide
8. History of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, bortezomib, boron, mannitol, or dexamethasone
9. = Grade 3 rash during prior thalidomide or lenalidomide therapy
10. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
11. Subjects with any one of the following:
• Clinically significant abnormal ECG finding at screening
• Congestive heart failure (New York Heart Association Class III or IV)
• Myocardial infarction within 12 months prior to starting study treatment
• Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
12. Subjects who received any of the following within the last 14 days of initiation of study treatment:
• Plasmapheresis
• Major surgery (kyphoplasty is not considered major surgery)
• Radiation therapy other than local therapy for myeloma associated bone lesions
• Use of any systemic anti-myeloma drug therapy
13. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
14. Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment.
15. Subjects unable or unwilling to undergo protocol required thromboembolism prophylaxis or herpes zoster prophylaxis will not be eligible to participate in this study
16. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
17. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
18. Pregnant or breastfeeding females
19. Known seropositive for or active viral infection with human immunodeficiency virus (HI

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

relapsed or refractory multiple myeloma (MM)
MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Imnovid 1 mg hard capsules

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Imnovid 2 mg hard capsules

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Imnovid 3 mg hard capsules

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Trade Name: Imnovid 4 mg hard capsules

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Velcade
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Trade Name: Dexamethasone Tablets BP 2.0 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Dexamethason-ratiopharm® 4 mg tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num

Primary Outcome(s)

Secondary Objective: To evaluate the safety and additional efficacy of POM + BTZ + LD-DEX versus BTZ + LD-DEX in subjects with relapsed or refractory MM

Primary end point(s): Progression-Free Survival (PFS)

Timepoint(s) of evaluation of this end point: PFS will be assessed by:
- Bone Marrow Aspiration and/or Biospy – Screening and as Clinically indicated or to confirm CR
- Quantitative Serum Immunoglobulins, serum-protein electrophoresis (sPEP), 24-hour urine protein electrophoresis, serum and urine immunofixation, serum free light-chain assay, and extramedullary plasmacytoma (EMPs) at Screening and Day 1 of each cycle and PFS Follow-up (if applicable). If EMPs are only assessable radiographically, scans are to be conducted at Screening, C3D1, every 3 cycles thereafter during treatment, at treatment discontinuation, every 63 days (3 cycles) during the PFS follow-up phase, at PFS follow-up phase discontinuation, and when clinically indicated to confirm response (> or = PR)
-Skeletal Surveys – Screening and when clinically indicated

Main Objective: To compare the efficacy of POM + BTZ + LD-DEX with BTZ + LD-DEX in subjects with relapsed or refractory MM

Secondary Outcome(s)

Secondary end point(s): -Overall Survival (OS)
-Safety (type, frequency, seriousness and severity of AEs, and relationship of AEs to study drug or comparator)
-Overall response rate (ORR) (using the International Myeloma Working Group Uniform [IMWG] response criteria)
-Duration of response

Timepoint(s) of evaluation of this end point: OS: All long-term follow-up phase subjects will be contacted four (4) times a year (every 3 months) to obtain survival status for at least 5 years after the last subject is randomized into the study, or longer if clinically indicated
Safety: i. AEs: After signing ICF and until 28 days after treatment discontinuation; ii. SPM: After signing ICF up to and including the long-term follow-up period and up to 5 years after last subject enrolled
Overall Response Rate (ORR): when assessable
Duration of Response: when assessable

Secondary ID(s)

CC-4047-MM-007

2014-000268-17-IE

NCT01734928

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date: 02/04/2015
Contact: