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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

Thank you

Trial Information

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


I. To establish the maximum tolerated dose of carfilzomib given in combination with oral
cyclophosphamide and thalidomide and dexamethasone. (Phase I) II. In newly diagnosed myeloma
to evaluate the response rate (CR, nCR, and VGPR) to carfilzomib given in combination with
oral cyclophosphamide and thalidomide and dexamethasone after four 28 day cycles. (Phase II)


I. Determine the overall response rate (CR, nCR, PR) after 4, 8, 12 cycles. II. Determine
the duration of progression-free and overall survival for patients receiving this regimen.

III. To evaluate the incidence of toxicities for this regimen. IV. To evaluate the ability
to successfully collect peripheral blood stem cells following four months of combination

OUTLINE: This is a phase I, dose escalation study of carfilzomib followed by a phase II

Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on
days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days
1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable

After completion of study treatment, patients are followed at 3 months, then every 3 months
for 1 year, and then every 6 months for up to 3 years.

Inclusion Criteria


- 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


- MGUS or smoldering myeloma

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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Maximum tolerated dose (phase I)

Outcome Time Frame:

From baseline to end of active treatment

Safety Issue:


Principal Investigator

Joseph R. Mikhael, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

Related Keywords:

  • Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



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Medical University of South Carolina Charleston, South Carolina  29425-0721
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404