A Multicenter Open label Phase 2 study of Carfilzomib Weekly plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma.

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-004490-10-BE

Enrollment

Registered

2013-07-09

Start date

2013-09-18

Completion date

Unknown

Last updated

2024-12-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

A Multicenter Open label Phase 2 study of Carfilzomib Weekly plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma. MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Interventions

Trade Name: Kyprolis Product Name: Carfilzomib (KYPROLIS) Product Code: PR171 Pharmaceutical Form: Powder for injection INN or Proposed INN: Carfilzomib CAS Number: 868540-17-4 Current Sponsor code: 2

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Must be able to understand and voluntarily sign an informed consent form 2. Must be able to adhere to the study visit schedule and other protocol requirements 3. Age ³ 65 years (at least 65 years of age or older) 4. Life expectancy > 6 months. 5. Patients must have Symptomatic Measurable previously Untreated MM, as defined below: 5.1. Symptomatic MM diagnostic criteria (all 3 required) • Monoclonal plasma cells in the bone marrow =10% • Monoclonal protein present in the serum and/or urine. • Myeloma-related organ dysfunction (at least one of the following)1 [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dL) [A] Anemia (hemoglobin 30% plasma cells are required in the bone marrow or proven plasmocytic infiltration in bone marrow biopsy 5.2. AND have measurable disease as defined by the following: Patients must have a clearly detectable and quantifiable monoclonal M-component value in the serum and/or urine. ? IgG (serum M-component > 10g/l) ? IgA (serum M-component > 5g/l) ? IgD (serum M-component > 0.5g/l) ? Light chain (serum M-component >1g/l or Bence Jones > 200mg/24H) ? Serum FLC assay: involved FLC level > 10 mg/dl provided serum FLC ratio is abnormal 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 7. Adequate bone marrow function, documented within 72 hours and without transfusion 5 days prior to the first intake of investigational product (C1J1) nor growth factor support, defined as: • Absolute neutrophils = 0.75 x109/L, • Untransfused Platelet count = 75 x109/L • Hemoglobine =8.5 g/L 8. Adequate organ function defined as: • Serum total bilirubin < 2.0 mg/dL • Clairance creatinine = 30ml/min • Serum SGOT/AST or SGPT/ALT < 2.5x upper limit of normal (ULN) 9. Subjects affiliated with an appropriate social security system. 10. Male subjects must: 10.1. Understand the potential teratogenic, and genotoxic risk of Melphalan if engaged in sexual activity with a pregnant female or a female of childbearing potential. 10.2. Understand the potential genotoxic risk of Carfilzomib if engaged in sexual activity with a pregnant female or a female of childbearing potential. 10.3. Practice complete abstinence or understand the need and agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential throughout the entire duration of study treatment, during dose interruptions and until at least 3 months after the end of treatment discontinuation of CMP, even if he has undergone a successful vasectomy. If pregnancy or a positive pregnancy test does occur in the partner of a male study patient during study participation, the investigator must be notified immediately. 10.4. Agree not to donate semen or sperm during study drug therapy and until at least 3 months after the end of treatment discontinuation of CMP. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for thi

Exclusion criteria

Exclusion criteria: 1. Any other uncontrolled medical condition or comorbidity that might interfere with subject’s participation. 2. Known positive for HIV or active infectious hepatitis, type B or C. 3. Patients with non-secretory MM and non-measurable MM 4. Patient with terminal renal failure that require dialysis and clairance creatinine grade 2 severity 11. Refusal to participate in the study 12. Persons protected by a legal regime (guardianship, trusteeship) 13. Alkeran’s (Melphalan) contraindication: Hypersensitivity to Melphalan or to any other constituents. 14. Patients with heart failure class 3 and 4 according to the NYHA criteria, or patients with past history of myocardial infarction within the last 6 months or no controlled cardiac conduction abnormalities. 15. Patients with a left ventricular ejection fraction under or equal to 30 % (LVEF = 30%). 16. Female of childbearing potential (Females are defined as not of childbearing potential if documentation of “Natural menopause for at least 24 consecutive months, a hysterectomy, or bilateral oophorectomy”).

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine MTD of Carfilzomib Weekly based on definition of DLTs ;Secondary Objective: • To determine the VGPR (Very Good Partial Response) + CR (complete response) rate of Carfilzomib weekly at the MTD + MP at the end of the 9 induction cycles • To determine the safety profile of Carfilzomib weekly +MP for the first 9 cycles and during maintenance. • To determine the safety profile of Carfilzomib Weekly according to doses in the first part of the study • To determine the response rate (Partial response and better), the stringent CR rate (sCR) and Immunophenotypic CR (MRD; Will be performed by in Nantes, France) during the first 9 cycles and during maintenance. • To determine the clinical benefit response rate (CBR, Minor response and better). • To determine the Progression-free Survival (PFS), Event-free Survival (EFS), and Time to Progression (TTP) • To determine the Overall Survival • To determine the Time to response and Response duration ;Primary end point(s): To determine MTD of Carfilzomib Weekly. If dose-limiting toxicities (DLTs) occur in fewer than 3 of these patients per cohort, the next cohort of 6 patients (cohort 2, 3 and 4) will be N+1 up to cohort 4. If at any time during cycle 1 of a dose cohort, > 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in >33% (i.e. > 2 of 6) subjects in a cohort. ;Timepoint(s) of evaluation of this end point: At the end of the study when the last patient will have relapsed	—

Measure

Time frame

Main Objective: To determine MTD of Carfilzomib Weekly based on definition of DLTs ;Secondary Objective: • To determine the VGPR (Very Good Partial Response) + CR (complete response) rate of Carfilzomib weekly at the MTD + MP at the end of the 9 induction cycles • To determine the safety profile of Carfilzomib weekly +MP for the first 9 cycles and during maintenance. • To determine the safety profile of Carfilzomib Weekly according to doses in the first part of the study • To determine the response rate (Partial response and better), the stringent CR rate (sCR) and Immunophenotypic CR (MRD; Will be performed by in Nantes, France) during the first 9 cycles and during maintenance. • To determine the clinical benefit response rate (CBR, Minor response and better). • To determine the Progression-free Survival (PFS), Event-free Survival (EFS), and Time to Progression (TTP) • To determine the Overall Survival • To determine the Time to response and Response duration ;Primary end point(s): To determine MTD of Carfilzomib Weekly. If dose-limiting toxicities (DLTs) occur in fewer than 3 of these patients per cohort, the next cohort of 6 patients (cohort 2, 3 and 4) will be N+1 up to cohort 4. If at any time during cycle 1 of a dose cohort, > 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in >33% (i.e. > 2 of 6) subjects in a cohort. ;Timepoint(s) of evaluation of this end point: At the end of the study when the last patient will have relapsed

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Secondary

Measure	Time frame
Secondary end point(s): •To determine the VGPR (Very Good Partial Response) + CR (Complete Response) rate of Carfilzomib Weekly at the MTD + MP at the end of the 9 induction cycles using International Myeloma Working Group (IMWG) response criteria •To determine the Safety profile (type, frequency, severity, and relationship of adverse events to study treatment). Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria for the first 9 cycles and during maintenance. • To determine the safety profile of Carfilzomib Weekly according to doses in the first part of the study • To determine the Overall Response rate [Partial (PR) and better] using IMWG response criteria and to determine the sCR rate using IMWG response criteria (12) during the first 9 cycles and during maintenance. • Minor response will be determined using EBMT criteria • To determine the Progression-free Survival (PFS, from the date of inclusion to the date of the progression); Event-free Survival (EFS, from the date of inclusion to the date of any event, progression, death or any other cause for end of treatment); Time to progression (TTP, from the date of inclusion to the date of the progression or death, whichever occurs first); Overall Survival (OS, from the date of inclusion to the date of the last news); • To determine the Time to response (TTR, from the date of inclusion to the date of the first observation of response) and Response duration (DOR, time between first documentation of response and disease progression) ;Timepoint(s) of evaluation of this end point: At the end of the study when the last patient will have relapsed	—

Measure

Time frame

Secondary end point(s): •To determine the VGPR (Very Good Partial Response) + CR (Complete Response) rate of Carfilzomib Weekly at the MTD + MP at the end of the 9 induction cycles using International Myeloma Working Group (IMWG) response criteria •To determine the Safety profile (type, frequency, severity, and relationship of adverse events to study treatment). Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Events (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria for the first 9 cycles and during maintenance. • To determine the safety profile of Carfilzomib Weekly according to doses in the first part of the study • To determine the Overall Response rate [Partial (PR) and better] using IMWG response criteria and to determine the sCR rate using IMWG response criteria (12) during the first 9 cycles and during maintenance. • Minor response will be determined using EBMT criteria • To determine the Progression-free Survival (PFS, from the date of inclusion to the date of the progression); Event-free Survival (EFS, from the date of inclusion to the date of any event, progression, death or any other cause for end of treatment); Time to progression (TTP, from the date of inclusion to the date of the progression or death, whichever occurs first); Overall Survival (OS, from the date of inclusion to the date of the last news); • To determine the Time to response (TTR, from the date of inclusion to the date of the first observation of response) and Response duration (DOR, time between first documentation of response and disease progression) ;Timepoint(s) of evaluation of this end point: At the end of the study when the last patient will have relapsed

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Countries

Belgium

Contacts

Public ContactBimetra Clinics

Ghent University Hospital

Bimetra.Clinics@uzgent.be+3293320500

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026