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Phase 2
65 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information


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

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.

Inclusion Criteria:

- Patient is of a legally consenting age as defined by local regulations.

- Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell

- Patient is, in the investigator(s) opinion, willing and able to comply with the
protocol requirements.

- Patient has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
medical care.

- Female patient is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.

- Male patient agrees to use an acceptable method for contraception (i.e., condom or
abstinence) for the duration of the study.

- Patient is a newly diagnosed MM patient.

- Patient has measurable disease, defined as follows: any quantifiable serum monoclonal
protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where
applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo
or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as
determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or
an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than
10% of patients admitted to this study will be oligo- or non-secretory MM with free
light chains only in order to maximize interpretation of benefit results.

- - Patient has a Karnofsky performance status ≥60%.

- Patient has a life-expectancy >3 months.

- Patient has the following laboratory values within 14 days before Baseline (day

1 of the Cycle 1, before study drug administration):

- Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is
> 50%) within 14 days prior to drug administration).

- Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors.

- Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)

- Alanine transaminase (ALT): ≤ 3 x the ULN.

- Total bilirubin: ≤ 2 x the ULN.

- Calculated or measured creatinine clearance: ≥ 15 mL/minute

Exclusion Criteria:

- - Patients with non-secretory MM, unless serum free light chains are present and the
ratio is abnormal.

- Pregnant or lactating females

- Patient has active infectious hepatitis type B or C or HIV.

- Patients with myocardial infarction or unstable angina ≤ 4 months or other clinically
significant heart disease (e.g., CHF NY Heart Association class III or IV,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen)

- Peripheral neuropathy > CTCAE grade 2 and ≥ grade 2 painful peripheral neuropathy
(with the difference being in the exclusion of patients with Grade 2 painful PN).

- Known history of allergy to Capsidol (a cyclodextrin derivative used to solubilize

- Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
drugs, or intolerance to hydration due to preexisting pulmonary or cardiac

- Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to baseline;

- Patient has any other clinically significant illness that would, in the
investigator's opinion, increase the patient's risk for toxicity.

- Patients with a prior malignancy within the last 5 years (except for basal or
squamous cell carcinoma, or in situ cancer of the cervix or breast, or localized
prostate cancer of Gleason score <7 with a stable PSA)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Description:

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.

Outcome Time Frame:

4 years

Safety Issue:



Italy: The Italian Medicines Agency

Study ID:




Start Date:

July 2011

Completion Date:

April 2015

Related Keywords:

  • Multiple Myeloma
  • carfilzomib
  • dexamethasone
  • cyclophosphamide
  • multiple myeloma
  • newly diagnosed
  • Multiple Myeloma
  • Neoplasms, Plasma Cell