A Phase 2 interventional study of CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE in Multiple Myeloma, sponsored by European Myeloma Network B.V.. Completed at 13 sites in 2 countries. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2023-09-08.
Sponsored by European Myeloma Network B.V. · Phase 2, Interventional, and Treatment
The purpose of this study is to determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed Multiple Myeloma (MM).
This protocol is a phase II multicenter, international, non-comparative, open label study designed to jointly assess the safety and the efficacy of the association Carfilzomib with Cyclophosphamide and Dexamethasone (CCd) as induction treatment and Carfilzomib alone as maintenance in newly diagnosed MM patients.
Patients will be evaluated at scheduled visits in up to 4 study periods: pre-treatment, treatment, maintenance and long-term follow-up.
The pre-treatment period includes screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above.
The treatment period includes administration of Carfilzomib, Cyclophosphamide and Dexamethasone for 9 4-week courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled Carfilzomib administration. The response will be assessed after each 4-week cycle.
The maintenance period includes carfilzomib alone on days 1, 2, 15, 16 at 36mg/m2. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator. It will be initiated at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years.
The Long Term Follow Up periods will start after development of confirmed Progression Disease, all patients are to be followed for survival during the Long Term Follow Up period every 3 months via telephone or office visit.
Approximately 15 Italian centers and foreign centers will participate to the protocol.
Patients with symptomatic newly diagnosed MM whose age is ≥ 65 years or who are ineligible for autologous stem cell transplantation. Up to 53 patients will be enrolled from different centers.
The duration of the treatment is approximately 9 months. This length of time is required to complete 9 courses of CCd. At the end of the first stage (19 patients), the trial will be temporarily stopped until all 19 patients complete the toxicity and efficacy evaluation (3 cycle): if there are more than 7 responses and less than 8 toxicities, a further group of 34 patients (total=53) will be enrolled. Otherwise, the trial will be definitively stopped or the DSMC will recommend testing other doses of the drugs.
The maintenance period in both phases will start at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years. The duration of follow-up from relapse will be approximately 2 years. The occurrence of PD will determine the duration of TTP of each patient. The occurrence of death will determine the duration of overall survival. The first analysis to evaluate safety and efficacy is planned when the 19 patients enrolled in the first stage of the study have completed the third cycle of induction treatment.
The trial will be stopped if there are \< 6 responses, or > 9 toxicities or the Data Safety Monitoring Committee recommends testing other doses of the drugs; Otherwise, a further group of 34 patients (total=53) will be enrolled. The final conclusion will be negative if there are ≤ 23/53 responses, or ≥ 20/53 drug-related toxicities.
3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.
This study's enrollment of 58 is above the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →European Myeloma Network B.V. is the lead sponsor of 19 studies on the registry; 4 are open to participants now.
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Patient has the following laboratory values within 14 days before Baseline (day
1 of the Cycle 1, before study drug administration):
Exclusion Criteria:
The treatment period includes administration of Carfilzomib Cyclophosphamide Dexamethasone for 9 courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled carfilzomib administration. The response will be assessed after each cycle.
Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
Drug pages: Carfilzomib · Cyclophosphamide · Dexamethasone
Patients will start induction treatment with Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. Low dose Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23. Carfilzomib = 20 mg/m2 IV once daily on days 1, 2, of cycle 1 only followed by 36 mg/ m2 days 8, 9, 15, 16 in cycle 1, then for all subsequent doses 36 mg/ m2 IV once daily on days 1, 2, 8, 9, 15, 16, followed by 13-day rest period (day 17 through 28). Each cycle will be repeated every 28 days for a total of 9 courses. MANTEINANCE PERIOD At the end of induction phase (9 courses), maintenance phase with Carfilzomib alone IV at 36 mg/ m2 IV on days 1, 2, 15, 16 will start, until progression or intolerance. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator, or the patient may be removed from the study
Toxicity: Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0)
Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity excluding anemia, (grade 4 neutropenia must last longer than 3 days and grade 4 thrombocytopenia must last longer than 7 days in order to be considered a toxicity) with the exception of (grade 4 neutropenia \> 3 days , or grade 4 thrombocytopenia \>7 days duration) or grade 3 non-hematologic drug-related toxicity.
Time frame: 4 years
Efficacy will be assessed by considering partial response (PR) following the proposed regimen. Assessment of Partial Response rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group.
Time frame: 4 years
Response rate
Time frame: 4 years
Duration of Progression Free Survival
Time frame: 4 years
Time to progression (TTP)
Time frame: 4 years
Duration of Response (DOR)
Time frame: 4 years
Duration of Overall Survival
Time frame: 4 years
Time to next therapy
Time frame: 4 years
Progressio Free Survival
Relation between responses and Progression Free Survival, in responding and non-responding patients.
Time frame: 4 years
β2-microglobulin as prognostic factors
Subgroups analysis on prognostic factors
Time frame: 4 years
peripheral neuropathy
Rates of peripheral neuropathy, according to the National Cancer Institute Common Toxicity Criteria (version 4.0)
Time frame: 4 years
Progression Free Survival
Effect on Progression Free Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)
Time frame: 4 years
C reactive protein as prognostic factors
Subgroups analysis on prognostic factors
Time frame: 4 years
cytogenetics as prognostic factors
Subgroups analysis on prognostic factors
Time frame: 4 years
microRNA
Subgroups analysis on prognostic factors
Time frame: 4 years
gene expression profile
Subgroups analysis on prognostic factors
Time frame: 4 years
Overall Survival
Effect on Overall Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)
Time frame: 4 years
Ran from Jul 2011 to primary completion in Oct 2012, 15 months.
Of 412 non-industry phase 2 interventional studies under Multiple Myeloma, half reached primary completion within 58 months of starting (the median), counting those still running; a quarter within 40 and three quarters within 95. This study's 15 months is below that.
Counting every sponsor, half of 502 studies reached it within 55 months; a quarter within 35 and three quarters within 90.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Carfilzomib · Cyclophosphamide · Dexamethasone
European Myeloma Network B.V.