A MULTICENTER, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS
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
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Italy: The Italian Medicines Agency