Study of Carfilzomib in Combination w/Dexamethasone in Patients w/Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Carfilzomib; Dexamethasone
Intervention MeSH terms: Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and tolerability of increasing doses of
      carfilzomib in combination with dexamethasone
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have newly diagnosed multiple myeloma immunoglobulin G (IgG),
             immunoglobulin A (IgA), immunoglobulin E (IgE) or immunoglobulin D (IgD) by the
             International Myeloma Foundation (IMF) 2003 Diagnostic Criteria

          -  Subjects must be treatment naïve.

          -  Patient must not have been previously treated with any prior systemic therapy for the
             treatment of multiple myeloma.

          -  Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does
             not disqualify the patient (the dose should not exceed the equivalent of 160 mg of
             dexamethasone in a 2 week period).

          -  Patients treated with local radiotherapy with or without concomitant exposure to
             steroids, for pain control or management of cord/nerve root compression, are eligible.

          -  One week must have lapsed since last date of radiotherapy, which is recommended to be
             a limited field.

          -  Patients who require concurrent radiotherapy should have entry to the protocol
             deferred until the radiotherapy is completed and one week have passed since the last
             date of therapy.

          -  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             not part of normal medical care, with the understanding that consent may be withdrawn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 subject at any time without prejudice to future medical care.

          -  All necessary baseline studies for determining eligibility must be obtained within 21
             days prior to enrollment.

          -  Age 18 years at the time of signing Informed Consent.

          -  Life expectancy of more than three months.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 or Karnofsky
             performance status of ≥ 60.

          -  Subject must be able to adhere to the study visit schedule and other protocol
             requirements.

          -  Written informed consent in accordance with federal, local, and institutional
             guidelines.

          -  Female subjects of child-bearing potential must have a negative serum pregnancy test
             within seven days of the first dose and agree to use dual methods of contraception
             during and for 3 months following last dose of drug.

          -  Post menopausal females (> 45 years old and without menses for > 1 year) and
             surgically sterilized females are exempt from a pregnancy test.

          -  Male subjects must use an effective barrier method of contraception during study and
             for three months following the last dose if sexually active with a female of
             child-bearing potential.

          -  Subjects must be able to receive outpatient treatment and laboratory monitoring at the
             institute that administers agent.

        Exclusion Criteria:

          -  Patient has > Grade 2 peripheral neuropathy on clinical examination within 14 days
             before enrollment.

          -  Renal insufficiency as measured by calculated creatinine clearance < 15 mL/min by
             Cockroft-Gault formula.

          -  Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
             (i.e., unable to maintain a platelet count 50,000 cells/mm³).

          -  Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may
             not be used to meet ANC eligibility criteria.

          -  Total bilirubin > 2.0 mg/dL or bilirubin ≥ 2 x upper limit of normal (ULN).

          -  Subjects with a hemoglobin < 8.0 g/dL (Transfusion are permitted).

          -  Alanine aminotransferase (ALT) (SGPT) > 2.5 x ULN.

          -  Aspartate aminotransferase (AST) ≥ 2.5 x ULN.

          -  Major surgery within three weeks of starting study drug (Cycle 1 Day 1).

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at screening has to be documented by the investigator as not medically
             relevant.

          -  Clinically relevant active infection requiring either oral or intravenous antibiotics
             or antifungal agents.

          -  Serious co-morbid medical conditions such as chronic obstructive or chronic
             restrictive pulmonary disease, and cirrhosis.

          -  Any condition, including laboratory abnormalities, that in the opinion of the
             Investigator places the subject at unacceptable risk if he/she were to participate in
             the study.

          -  Prior malignancy (within the last 3 years) except for adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ
             prostate cancer or if the expected survival from other malignancy is less than 90% at
             5 years.

          -  Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).

          -  Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy,
             organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).

          -  Known HIV infection.

          -  Known active hepatitis B or C viral infection.

          -  Plasma cell leukemia.

          -  Glucocorticoid therapy (prednisone > 20 mg/day or equivalent) within the last three
             weeks.

          -  Any prior treatment for multiple myeloma with standard regimens or investigative
             regimens.

          -  Subjects with treatment related myelodysplastic syndrome.

          -  Subjects in whom the required program of oral and intravenous fluid hydration is
             contraindicated, e.g., due to pre-existing significant pulmonary, cardiac or renal
             impairment.

          -  Subjects with known primary amyloidosis.

          -  Female subject is pregnant or breast-feeding.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.