Carfilzomib and Dexamethasone in Treating Patients With Multiple Myeloma Who Previously Underwent a Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To assess the complete response (CR) rate with carfilzomib and dexamethasone
consolidation following an upfront single stem cell transplant (SCT).

SECONDARY OBJECTIVES:

I. To assess the toxicity of carfilzomib and dexamethasone when used as consolidation
therapy in patients post SCT.

II. To determine the progression free rate at 1 and 2 years post SCT. III. To evaluate
progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To determine the proportion of patients achieving a minimal residual disease (MRD)
negative status.

II. To assess the HevyLite assay prior to and during treatment.

OUTLINE:

Patients receive carfilzomib intravenously (IV) over 30 minutes and dexamethasone orally
(PO) on days 1, 2, 15, and 16. Treatment repeats every 28 days for 6 courses in the absence
of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 3 years and
then every 6 months for 2 years.

Inclusion Criteria:

- Creatinine =< 3 mg/dL

- Absolute neutrophil count >= 1,000/uL

- Platelet count >= 75,000/uL

- Hemoglobin >= 8.0 g/dL

- Previous diagnosis of symptomatic multiple myeloma (MM)

- Received single autologous stem cell transplantation 60-120 days prior to
registration

- Received the autologous SCT =< 12 months of their diagnosis of myeloma to be eligible
for the study

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Recovered from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and
hematological toxicity)

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that the subject may withdraw
consent at any time without prejudice to future medical care

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

- Willingness to return to one of the enrolling institutions for follow-up (during the
active monitoring phase of the study); NOTE: during the active monitoring phase of a
study (i.e., active treatment and observation), participants must be willing to
return to the consenting institution for follow-up

- Measurable disease of multiple myeloma at the time of baseline values for disease
assessment as defined by at least one of the following:

- Serum monoclonal protein >= 1.0 g/dL

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

- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- NOTE: for patients with no relapse prior to transplant, measurable disease at
the time of diagnosis

- NOTE: for patients who have had a disease relapse prior to transplant,
measurable disease at the time of the most recent relapse immediately prior to
transplant; NOTE: if the patient had treatment for the relapsed disease prior to
transplant, the patient must have measurable disease at the time of relapse
prior to this therapy

- Willing to provide bone marrow and blood samples for correlative research purposes

Exclusion Criteria:

- Prior allogeneic bone marrow/peripheral blood stem cell transplant

- Evidence of disease progression post SCT at the time of consideration for the study
enrollment

- Myocardial infarction =< 6 months prior to registration

- New York Heart Association (NYHA) class III or IV heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmias

- Electrocardiographic (ECG) evidence of acute ischemia or active conduction system
abnormalities; NOTE: prior to study entry, any ECG abnormality at screening has to be
documented by the investigator as not medically relevant

- Seroreactivity for human immunodeficiency virus (HIV), human T-cell lymphotrophic
virus (HTLV) I or II, hepatitis B virus (HBV), or hepatitis C virus (HCV)

- Other active malignancy requiring therapy; EXCEPTIONS: non-melanotic skin cancer or
carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy,
they must not be receiving other specific treatment for their cancer

- Pregnant women or women of reproductive capability 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 28 days after
stopping treatment

- Other co-morbidity, which would interfere with patient's ability to participate in
the trial, e.g. uncontrolled infection, uncompensated lung disease

- 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

- Known allergies to any of the components of the investigational treatment regimen or
required ancillary treatments