Clinical trial NCT02056756 (phase 1/phase 2, status: active, not recruiting)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: carfilzomib
SMILES: CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
Eligibility criteria:

        Inclusion Criteria:

          -  Patient ≥ 18 years old.

               -  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                  that consent may be withdrawn by the patient at any time without prejudice to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 commits
                  continued abstinence from heterosexual intercourse during the duration of the
                  study or is willing to use two methods of birth control, one highly effective
                  method and one additional effective method at the same time, at least 4 weeks
                  before starting carfilzomib and bendamustine therapy, during carfilzomib and
                  bendamustine therapy and for at least 4 weeks after stopping carfilzomib and
                  bendamustine therapy. Highly effective methods are hormonal contraceptives (birth
                  control pills, injections, and implants), intrauterine device, tubal ligation and
                  partner's vasectomy. Additional effective methods are condom, diaphragm, and
                  cervical cap. Women with child bearing potential must have two negative pregnancy
                  tests (sensitivity at least 50 mIU/mL) prior starting carfilzomib and
                  bendamustine therapy. The first pregnancy test must be performed 10 - 14 days and
                  the second within 24 hours before starting carfilzomib and bendamustine therapy.
                  Pregnancy testing for the first 4 weeks of study therapy must be performed weekly
                  and thereafter every 4 weeks if menstrual cycles are regular or every 2 weeks if
                  menstrual cycles are irregular.

               -  Male patient agrees to use an acceptable method for contraception (i.e., condom
                  or abstinence) for the duration of the study and for 6 months after stopping
                  study therapy.

               -  Patient with relapsed or/and refractory multiple myeloma after failure of two or
                  more treatment regimens (previous bortezomib is allowed).

               -  Patient has measurable disease, defined as follows: any quantifiable serum
                  monoclonal protein (M-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 >6 months.

               -  Patient has the following laboratory values within 14 days before Baseline (day 1
                  of the Cycle 1, before study drug administration):

          -  Platelet count ≥70 x 109/L (≥50 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/min (or, as alternative serum
             creatinine <2 mg/dL).

          -  LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of
             evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available
             (not applicable in Germany).

        Exclusion Criteria:

          -  Pregnant or lactating females

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

               -  Patients with active congestive heart failure (New York Heart Association [NYHA]
                  Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled
                  by conventional intervention.

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

               -  Known history of allergy to Captisol (a cyclodextrin derivative used to
                  solubilize carfilzomib)

               -  Known history of intolerability to high dose dexamethasone

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

               -  Subject 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.

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