A Phase I/II Trial of Cyclophosphamide, Carfilzomib, Thalidomide and Dexamethasone (CYCLONE) in Patients With Newly Diagnosed Active Multiple Myeloma

Inclusion Criteria

Inclusion

- Creatinine =< 2 mg/dL

- Calculated Creatinine Clearance >= 30 mL/min

- Total Bilirubin =< 2.0 mg/dL

- Alkaline Phosphatase =< 3 x ULN

- ALT =< 3 x ULN

- Absolute neutrophil count >= 1000/uL

- Platelet >= 75000/uL

- Hemoglobin >= 8.0 g/dL

- Untreated symptomatic myeloma: Prior non-systemic therapy for the treatment of
solitary plasmacytoma is permitted, but >= 1 month should have elapsed from the last
day of radiation; prior therapy with clarithromycin, DHEA, anakinra, pamidronate or
zoledronic acid is permitted; any additional agents not listed must be approved by
the Principal Investigator

- Prior high dose corticosteroid therapy for twelve days (480 mg total dose) or less is
permitted for emergent complications from newly diagnosed multiple myeloma

- Measurable disease of multiple myeloma, as defined by at least ONE of the following:

- Serum monoclonal protein >= 1.0 g by protein electrophoresis

- OR > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

- OR serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio; OR monoclonal bone marrow
plasmacytosis >= 30% (evaluable disease)

- ECOG performance status (PS) 0, 1, 2; ECOG PS of 3 will be allowed if secondary to
pain in the opinion of the Investigator

- Willingness and able to provide informed written consent

- Negative serum pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Willingness to return to Mayo Clinic enrolling institution for follow-up

Exclusion

- MGUS or smoldering myeloma

- Peripheral sensory neuropathy >= Grade 2 as defined by CTEP Active Version of the
CTCAE

- Active malignancy with the exception of non melanoma skin cancer or in situ cervical
or breast cancer

- Pregnant women or women of reproductive ability who are unwilling to use effective
contraception

- Nursing women

- Men who are unwilling to use a condom (even if they have undergone a prior vasectomy)
while having intercourse with any woman, while taking the drug and for 4 weeks after
stopping treatment

- Known hypersensitivity, allergy or inability to tolerate any of the agents employed

- Active, uncontrolled infection

- Severe cardiac comorbidity

- New York Heart Association Class III or IV Heart Failure

- Recent history of myocardial infarction in the six months prior to registration

- Uncontrolled angina or electrocardiographic evidence of acute ischemia

- Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of
active conduction system abnormalities

- Cardiac amyloidosis with hypotension (systolic BP less than 100 mmHg)

- Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered
investigational; NOTE: Bisphosphonates are considered to be supportive care rather
than therapy, and are thus allowed while on protocol treatment

- The following medications are not permitted during the trial: any other
investigational treatment; any cytotoxic chemotherapy; any other systemic
anti-neoplastic therapy including, but not limited to, immunotherapy, hormonal
therapy, or monoclonal antibody therapy

- Palliative radiation therapy is permitted if clinically indicated and not indicative
of progressive disease