Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma
Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With High-Risk Multiple Myeloma
This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in
 treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer
 cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,
 such as pomalidomide and 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, pomalidomide, and dexamethasone may work better in treating
 patients with multiple myeloma.
PRIMARY OBJECTIVE:

 I. To determine the ≥ complete response (CR) rates with carfilzomib, pomalidomide and
 dexamethasone (CPd) maintenance.

 SECONDARY OBJECTIVES:

 I. To determine the improved progression free survival (PFS) with CPd maintenance among
 high-risk patients.

 II. To determine the best response rates (very good partial response rate [VGPR], stringent
 complete response [sCR] rate) with CPd maintenance.

 II. To evaluate the safety of the CPd combination as maintenance regimen.

 III. To characterize safety in subjects who receive CPd maintenance.

 IV. To evaluate the duration of response (DOR).

 V. To evaluate the overall survival (OS) in high-risk patients.

 VI. To evaluate the minimal residual disease (MRD) detection with CPd maintenance.

 OUTLINE:

 Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15,
 pomalidomide orally (PO) daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15.
 Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up every 3 months.
Inclusion Criteria:

 -  Patients must meet the following criteria on screening examination to be eligible to
 participate in the study; all laboratory assessments should be performed within 28
 days of initiation of protocol therapy unless otherwise specified; subject is, in the
 investigator's opinion, willing and able to comply with the protocol requirements

 -  Subject has given voluntary signed written informed consent before performance of any
 study-related procedure that is not part of normal medical care, with the
 understanding that consent may be withdrawn by the subject at any time without
 prejudice to their future medical care

 -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

 -  Subject is a transplant-eligible patient that have undergone autologous stem cell
 transplant (ASCT) within one year of their diagnosis and have achieved ≥ partial
 response (PR) based on International Myeloma Working Group (IMWG) standard criteria

 -  Patients with high risk disease defined as

 -  Presence of del(17p); t(4;14); t(14;16); t(14;20) by fluorescence in situ
 hybridization (FISH) or by cytogenetics (CTG)

 -  Plasma cell leukemia at diagnosis with ≥ 20% circulating plasma cells on
 peripheral blood

 -  Subject agrees to refrain from blood donations during therapy on study and for 90 days
 after therapy is completed

 -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
 test with a sensitivity of at least 50 milli-International units (mIU)/mL within 10-14
 days prior to and again within 24 hours of starting pomalidomide and must either
 commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
 methods of birth control, one highly effective method and one additional effective
 method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide
 through 90 days after the last dose of study drug; FCBP must also agree to ongoing
 pregnancy testing; men must agree to use a latex condom during sexual contact with a
 FCBP even if they have had a vasectomy from the time of signing the informed consent
 form through 90 days after the last dose of study drug; all patients must be
 registered in and must comply with all requirements of the pomalidomide Risk
 Evaluation and Mitigation Strategies (REMS) program; male subjects should refrain from
 sperm donation for at least 90 days after the last dose of carfilzomib or pomalidomide

 -  FCBP refers to sexually mature female, regardless of sexual orientation or
 whether they have undergone tubal ligation, who: 1) has not undergone a
 hysterectomy or bilateral oophorectomy; or 2) has not been naturally menopausal
 for at least 24 consecutive months

 Exclusion Criteria:

 -  Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined
 significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly,
 endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis
 or standard risk myeloma or secondary plasma cell leukemia

 -  High risk patients that did not achieve ≥ PR after stem cell transplant

 -  Participant has ≥ grade 2 peripheral neuropathy on clinical examination within 21 days
 before initiation of protocol therapy

 -  Creatinine clearance < 30 mL/min (either actual or calculated value), within 21 days
 of initiation of protocol therapy; the Cockcroft-Gault formula should be used for
 calculating creatinine clearance values

 -  Platelet count < 75,000 cells/mm³ at time of screening evaluation; transfusion may not
 be used to meet platelet eligibility criteria within 7 days of obtaining screening
 evaluation

 -  Participants with an absolute neutrophil count (ANC) < 1000 cells/mm³ at time of
 screening evaluation; growth factors may not be used to meet ANC eligibility criteria
 within 14 days of obtaining screening evaluation

 -  Participants with hemoglobin level < 8.0 g/dL, at time of screening; transfusion may
 not be used to meet eligibility criteria within 7 days of obtaining screening
 evaluation

 -  Bilirubin > 1.5 x institutional upper limit of normal (ULN), within 21 days of
 initiation of protocol therapy

 -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]),
 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]), or
 alkaline phosphatase > 3 x institutional ULN, within 21 days of initiation of protocol
 therapy

 -  Other ongoing or prior anti-myeloma therapy; patients may be receiving concomitant
 therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but
 no more than 10 mg p.o. once daily [q.d.] or its equivalent) for symptom management
 and comorbid conditions; doses of corticosteroid should be stable for at least 7 days
 prior to study treatment)

 -  Known significant cardiac abnormalities including:

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

 -  Uncontrolled angina, arrhythmia or hypertension

 -  Myocardial infarction within the past six months

 -  Any other uncontrolled or severe cardiovascular condition

 -  Prior cerebrovascular event with residual neurologic deficit

 -  Serious, intercurrent illness including, but not limited to, clinically relevant
 active infection, known active hepatitis B or C viral infection, known human
 immunodeficiency virus (HIV) infection, uncontrolled diabetes mellitus, or serious
 co-morbid medical conditions such as 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 5 years) except for adequately treated basal cell or
 squamous cell skin cancer, or in situ cervical cancer

 -  Known hypersensitivity to acyclovir or similar anti-viral drug

 -  Known intolerance to steroid therapy

 -  Contraindication or prior intolerance to thromboembolic prophylaxis with aspirin,
 warfarin or low-molecular weight heparin

 -  Participants with known central nervous system (CNS) disease

 -  Poor tolerability or known allergy to any of the study drugs or compounds of similar
 chemical or biologic composition to dexamethasone, boron or mannitol

 -  Female participants pregnant or breast-feeding

 -  Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug
 or who have not recovered from side effects of the surgery

 -  Participants with any significant history of non-compliance to medical regimens or
 unwilling or unable to comply with the instructions given to him/her by the study
 staff