S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma
Condition: Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Carfilzomib; Dexamethasone; Laboratory Biomarker Analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Ichthammol; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: carfilzomib; relapsed; refractory; multiple myeloma

Summary:

      This randomized phase II trial compares how well two different doses of carfilzomib work when
      given with dexamethasone in treating patients with multiple myeloma that has come back after
      a period of improvement or has not responded to treatment. Carfilzomib may stop the growth of
      cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving carfilzomib together with dexamethasone may kill more cancer cells. It is
      not yet known whether a higher or lower dose of carfilzomib works better when given with
      dexamethasone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  REGISTRATION STEP 1: INITIAL RANDOMIZATION

          -  Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be
             currently relapsed or refractory; all tests for establishing disease status must be
             completed within 28 days prior to registration and documented on the Baseline Tumor
             Assessment Form for Multiple Myeloma

          -  Patients must have measurable disease within 28 days prior to registration

          -  Patients must have received at least one prior regimen of chemotherapy for symptomatic
             multiple myeloma; patients may not have more than six (6) previous regimens of therapy
             for the disease; prior chemotherapy must have been completed at least 21 days prior to
             registration; for study purposes, a regimen is defined as follows:

               -  An anti-myeloma therapy used at the time of initial diagnosis or documented
                  disease progression which is given with the intent to decrease disease burden

               -  Any maintenance therapy used after an Induction should be considered part of that
                  Induction regimen

               -  Use of any agent or combination of agents more than once during the patient's
                  disease history for separate documented disease progressions will be counted as
                  separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial
                  diagnosis and achieves response, but then progresses and receives
                  lenalidomide/bortezomib after progression, these count as 2 separate regimens)

               -  In cases of allogeneic or autologous stem cell transplant, the entire induction +
                  stem cell mobilization + conditioning + planned maintenance should be considered
                  one regimen

          -  Patients may not have received any prior carfilzomib treatment

          -  Patients must not be receiving any other concurrent therapy considered to be
             investigational; patients must not be planning to receive any radiotherapy (except
             localized radiation for palliative care); patients must not be planning to receive any
             concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative
             intent

          -  Patients must have complete history and physical examination within 28 days prior to
             registration

          -  Patients must have baseline PET scan within 28 days prior to registration; note that
             images are submitted centrally for review

          -  Patients with non-secretory MM or known primary amyloidosis are not eligible

          -  Patients must have Zubrod performance status 0-2

          -  Patients must not have clinically significant illness including uncontrolled, active
             infection requiring intravenous antibiotics, New York Heart Association (NYHA) class
             III or class IV heart failure, unstable angina pectoris, myocardial infarction within
             the past 6 months, or >= grade 3 cardiac arrhythmias

          -  Patients must have undergone an electrocardiogram (EKG) within 28 days prior to
             registration

          -  Patients must have either echocardiogram (ECHO) with ejection fraction >= 45% within
             28 days prior to registration

          -  Patients must not have > grade 2 neuropathy and/or POEMS syndrome (plasma cell
             dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
             transaminase (SGPT) =< 3 x ULN

          -  Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support
             within 14 days prior to registration

          -  Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50%
             or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50%
             within 14 days prior to registration

          -  Calculated or measured creatinine clearance >= 30 ml/min within 14 days prior to
             registration

          -  Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible
             providing they meet all of the following additional criteria within 28 days prior to
             registration:

               -  Cluster of differentiation (CD)4 cells >= 500/mm^3

               -  Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on
                  combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on
                  cART

               -  No zidovudine or stavudine as part of cART

               -  Patients who are HIV+ and do not meet all of these criteria are not eligible for
                  this study

          -  Patients with known hepatitis B or hepatitis C infection must have viral load <
             800,000 IU/L within 28 days prior to registration

          -  Patients must have baseline skeletal survey to document lytic lesions, osteopenia or
             compression fracture within 28 days prior to registration

          -  Patients may have received palliative external beam radiation therapy (XRT) for local
             disease control with no curative intent. XRT must be completed at least 7 days prior
             to registration

          -  Patients must be offered participation in specimen submission for translational
             medicine studies and banking; with patient consent, specimens must be submitted

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for three years

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system

          -  REGISTRATION STEP 2: CROSSOVER

          -  Patient must have been eligible for and initially randomized to Arm 1 (low dose
             carfilzomib), begun cycle 2 of treatment, and progressed prior to completing 12 cycles
             of protocol therapy

          -  At least 14 days and no more than 28 days must have elapsed between the last day of
             treatment on Arm 1 and registration to Arm 3

          -  Patients must have recovered from all non-hematologic toxicities to =< grade 2 and
             from all hematologic toxicities to =< grade 3 prior to registration

          -  Patients must have begun cycle 2 (carfilzomib - 27 mg/m^2) and must not have received
             any dose reduction for toxicity in the last cycle of treatment, immediately preceding
             progression

          -  Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light
             chain testing performed within 14 days prior to registration in order to establish
             baseline measurements

          -  Patients must not have ejection fraction decrease > 10% from baseline (as determined
             by ECHO) or other ejection fraction decrease accompanied by other clinical
             signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure,
             measured within 28 days prior to registration; if any question exists regarding
             individual patient eligibility in this situation, contact the study chair for
             determination