- Males or females, age 18 years or older.
- Diagnosis of MM and documentation of treatment with an IMiD® and proteasome
inhibitor. Must have had 2 prior regimens/lines of therapy but there is no maximum
number of prior regimens and prior autologous bone marrow transplant is acceptable if
> 12 weeks from transplantation. A line of therapy is defined as a course of therapy
that is not interrupted by progressive disease. For example, induction therapy,
autologous stem cell transplantation, and maintenance therapy without intervening
progressive disease is one line of therapy.
- Confirmed evidence of relapse/disease progression from immediately prior MM therapy
or refractory to the immediately prior treatment. Refractory disease is defined as
those who are non-responsive (< minimal response) on active therapy or experience
disease progression within 60 days after the discontinuation of therapy. Relapsed
disease is defined as achievement of at least a minimal response followed by disease
progression on therapy or within 60 days of discontinuing active therapy.
- Patients may have received prior Carfilzomib (sensitive, relapsed and refractory all
eligible) but must be > 4 weeks from last dosing of Carfilzomib. In the expansion
cohort, at least 10 patients will be required to be refractory to Carfilzomib
(refractory defined as having evidence of disease progression while receiving
Carfilzomib or within 60 days of stopping Carfilzomib therapy).
- Patients must have measurable disease defined as at least one of the following:
- Serum M-protein ≥0.5 g/dl (≥5 g/l)
- Urine M-protein ≥200 mg/24 h
- Serum FLC assay: Involved FLC level ≥10 mg/dl (≥100 mg/l) and an abnormal serum free
light chain ratio (<0.26 or >1.65)
- Quantitative immunoglobulin > 500mg/dL, only for IgA and IgD myeloma when the protein
electrophoresis under-represents disease burden.
- Biopsy proven plasmacytoma (should be measured within 28 days prior to initial
investigational agent dosing).
- Subject has an ECOG ≤ 2 performance status OR Karnofsky ≥ 60% performance status.
- Females of childbearing potential (FCBP) - A female of childbearing potential is a
sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
months may be included if the patient is not pregnant by a negative serum β-human
chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening.
Pregnancy testing is not required for post-menopausal or surgically sterilized women.
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 successful
vasectomy. Females must agree to avoid pregnancy during the study and must agree to
use a medically acceptable method of birth control as determined by the study doctor
while participating in the study and for at least 12 weeks after the last dose of
- Voluntary written informed consent before performance of any study-related procedure
not part of routine medical care with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.
- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information (in accordance
with national and local subject privacy regulations).
Inclusion Clinical Laboratories Criteria
- The following laboratory results must be met within 7 days of study drug (treatment)
- Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 10e9/L) (Growth factor cannot
be used within the previous 7 days)
- Hemoglobin ≥ 8.0 g/dl (without transfusion within the previous 7 days).
- Platelet count > 50,000 cells/dL (50 x 10e9/L)
- Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault equation)
- Serum SGOT/AST or SGPT/ALT < 2.5 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN
- Serum calcium (corrected for albumin) level at or below the ULN range (treatment of
hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal
with standard treatment) prior to study therapy initiation.
- Left ventricular ejection fraction; LVEF ≥40% (By echocardiogram or MUGA testing).
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, low-risk prostate cancer after curative therapy or
complete resection of other advanced malignancy with the expectation that the patient
has received curative therapy.
- Patient has received other investigational drugs with 21 days before enrollment (or
must be > than four half-lives of the experimental agent). No prior SAR650984
anti-CD38 antibody therapy allowed.
- History of significant cardiovascular disease unless the disease is well-controlled
or history of myocardial infarction in the past 6 months. Significant cardiac
diseases includes second/third degree heart block; significant conduction
abnormalities, significant ischemic heart disease; QTc interval > 480 msec at
baseline (using Bazett's formula and read by local cardiologist); poorly controlled
hypertension; congestive heart failure of New York Heart Association (NYHA) Class II
or worse (slight limitation of physical activity; comfortable at rest, but ordinary
physical activity results in fatigue, palpitation, or dyspnea) and inability to
tolerate intravenous hydration necessary for study therapy administration.
- Prior peripheral stem cell transplant within 12 weeks of the first dose of study
- Daily requirement for corticosteroids (>10 mg prednisone QD or equivalent)
- Patients with evidence of significant mucosal or internal bleeding
- Prior radiation therapy or chemotherapy within 2 weeks or major surgical procedure
within 4 weeks of the first dose of study treatment.
- Known active infection requiring parenteral or oral anti-infective treatment, once a
patient has completed antibiotics and symptoms of infection have resolved to <Grade
2, they are then considered eligible from an infection standpoint.
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse follow-up evaluation.
- Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient. Examples of such conditions include any pre-existing kidney
disease (acute or chronic, unless renal insufficiency is felt to be secondary to MM),
hypertension, active seizure disorder or pulmonary diseases that would impose
excessive risk to the patient.
- Patient has hypersensitivity to any of the components of study therapy including
required prophylactic medications.
- Known HIV seropositivity or active hepatitis B or C viral infection
- Neuropathy ≥Grade 3 or painful neuropathy ≥Grade 2 (National Cancer Institute Common
Terminology Criteria for Adverse Events [NCI CTCAE] v4.03)
- Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral
medication, requirement for intravenous (IV) alimentation, active peptic ulcer or
prior surgical procedures or bowel resection affecting absorption.