ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma (ABC-103)
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring sphingosine kinase 2 inhibitor, sphingosine kinase 2, SK2 inhibitor, SK2
Eligibility Criteria
Inclusion Criteria:
- Patient must have a diagnosis of symptomatic multiple myeloma, relapsed or refractory after previous treatment with a proteasome inhibitor (bortezomib or carfilzomib) and an immunomodulatory agent (thalidomide, lenalidomide or pomalidomide).
Have measurable disease as defined by at least one of the following:
- Serum monoclonal (M) protein ≥1.0 g/dl by protein electrophoresis
- >200 mg of M 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
- Monoclonal bone marrow plasmacytosis ≥30%
- Voluntary signed and dated institutional review board (IRB) approved informed consent form in accordance with regulatory and institutional guidelines.
- Time interval from last systemic chemotherapy (not including low dose dexamethasone) more than 2 weeks prior to initiation of ABC294640. Patients receiving high dose dexamethasone defined as 40mg dexamethasone a day for 4 days will need 2 weeks washout prior to initiation of ABC294640
- 18 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Acceptable liver function:
- Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 1 baseline)
- AST (aminotransferase) (SGOT), ALT (alanine aminotransferase) (SGPT) ≤ 5 x ULN (CTCAE Grade 2 baseline)
- Serum creatinine ≤1.5 XULN (1.5 times the upper limit of normal) (CTCAE Grade 1 baseline)
Acceptable hematologic status (with or without transfusion support):
- Absolute neutrophil count ≥1000 cells/mm3,
- Platelet count ≥50,000 (plt/mm3),
- Hemoglobin ≥9 g/dL.
- Urinalysis: No clinically significant abnormalities.
- PT (partial thromboplastin) and PTT (partial thromboplastin time) ≤ 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT.
- As determined by the treating investigator, the patient must have well-controlled blood pressure, defined as systolic blood pressure <150mmHg (Millimeter of Mercury)and/or diastolic blood pressure <100 mmHg for the majority of measurements.
- A negative pregnancy test (if female of child bearing potential).
- For men and women of child-producing potential, willingness to use effective contraceptive methods during the study.
Exclusion Criteria:
- Pregnant or nursing women.
- Patients who are currently participating in any other clinical trial of an investigational product.
- Major surgery within 30 days prior to start of treatment
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to start of treatment
- Known human immunodeficiency virus infection
- Active hepatitis B or C infection with abnormal liver functions (i.e., LFTs (liver function test) > 2 x upper normal limits)
- Unstable angina or myocardial infarction within 4 months prior to start of treatment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to start of treatment
- Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to initiation of ABC294640
- Any other clinically significant medical or psychiatric disease or condition, or social situation that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Experimental
Phase Ib/II
For Phase Ib, the planned ABC294640 (Opaganib) doses for the escalation phase are: 250, 500, and 750 mg BID given continuously. The dose will be given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment. For phase II study, the patients will be treated with single agent ABC294640 at the MTD determined from the phase IB study (or at the highest dose used, if MTD is not reached) until disease progression or intolerable toxicity occurs in an individual patient.