| Eligibility |
Inclusion Criteria:
- Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy
• Prior treatment of hypercalcemia or spinal cord compression or active and/or
aggressively progressing myeloma with corticosteroids or lenalidomide or
bortezomib-based regimens does not disqualify the patient (the treatment dose should
not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more
than 1 cycle of Proteasome Inhibitor / Immunomodulatory-based therapy)
- Both transplant and non-transplant candidates are eligible.
- Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working
Group (IMWG) uniform criteria prior to initial treatment
- Monoclonal plasma cells in the Bone Marrow (BM) = 10% or presence of a biopsy-proven
plasmacytoma
- Measurable disease, prior to initial treatment as indicated by one or more of the
following:
- Serum M-protein = 1 g/dL
- Urine M-protein = 200 mg/24 hours
- If serum protein electrophoresis is felt to be unreliable for routine M-protein
measurement, then quantitative immunoglobulin levels are acceptable
- Serum freelite measurable disease as per current IMWG criteria
- Bone marrow specimen will be required at study entry; available DNA sample from
pre-induction BM will be used for calibration step for MRD evaluation by gene
sequencing.
- Males and females = 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate hepatic function, with bilirubin = 1.5 x upper limit of normal (ULN) and
aspirate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x ULN
- Absolute Neutrophil Count (ANC) = 1.0 x 109/L, hemoglobin = 8 g/dL, platelet count =
75 x 109/L.
- Calculated creatinine clearance (by Cockroft-Gault) = 50 mL/min or serum creatinine
below 2 g/dL
- Woman of childbearing potential must have 2 negative pregnancy tests prior to
initiating lenalidomide.
- Woman of childbearing potential must agree to use 2 reliable forms of contraception
simultaneously or to practice complete abstinence from heterosexual intercourse during
the following time periods related to this study: 1) for at least 28 days before
starting lenalidomide; 2) while participating in the study; and 3) for at least 30
days after discontinuation from the study.
- Male subjects must agree to use a latex condom during sexual contact with females of
childbearing potential while participating in the study and for at least 90 days
following discontinuation from the study even if he has undergone a successful
vasectomy.
- All study participants in the US must be consented to and registered into the
mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be
willing and able to comply with the requirements of Revlimid REMS®.
- Voluntary written informed consent.
Exclusion Criteria:
- Frail non-transplant candidates, defined as in Palumbo et al, Blood 2015.
- Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as
<1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, and no measurable disease
as per IMWG by Freelite.
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes)
- Amyloidosis
- Plasma cell leukemia
- Waldenström's macroglobulinemia or Immunoglobulin M-producing (IgM) myeloma
- Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of
protocol treatment (localized radiotherapy to a single site at least 1 week before
start is permissible)
- Participation in an investigational therapeutic study within 3 weeks or within 5 drug
half-lives (t1/2) prior to first dose, whichever time is greater
- Potential subjects with evidence of progressive disease as per IMWG criteria
- Patients not able to tolerate daratumumab, carfilzomib, lenalidomide or dexamethasone
- Peripheral neuropathy = Grade 2 at screening
- Diarrhea > Grade 1 in the absence of antidiarrheals
- Central Nervous System (CNS) involvement
- Pregnant or lactating females
- Major surgery within 3 weeks prior to first dose.
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association
(NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
conduction system abnormalities
- Prior or concurrent pulmonary embolism
- Known moderate or severe persistent asthma or known chronic obstructive pulmonary
disease (COPD)
- Known or suspected chronic obstructive pulmonary disease (COPD) with a forced
expiratory volume in 1 second (FEV1) <50% of predicted normal
- Moderate or severe persistent asthma within the past 2 years, or currently has
uncontrolled asthma of any classification. Note that subjects who currently have
controlled intermittent asthma or controlled mild persistent asthma are allowed
in the study.
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG
during screening
- Uncontrolled hypertension or diabetes
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two
weeks prior to first dose
- Known seropositive for or active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
seropositive because of hepatitis B virus vaccine are eligible.
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3
years except a) adequately treated basal cell, squamous cell skin cancer, thyroid
cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with
stable prostate specific antigen levels or cancer considered cured by surgical
resection alone
- Any clinically significant medical disease or condition that, in the Investigator's
opinion, may interfere with protocol adherence or a subject's ability to give informed
consent.
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