Inclusion Criteria:
1. Male or female, age 18 years or older. 2. A prior diagnosis of MM with documented disease progression. 3. 2
- - 4 prior lines of therapy.
4. Measurable disease defined as any of the following:
- - Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP).
- - ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine
electrophoresis (UPEP)
- Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free
light chain ratio.
5. Life expectancy of ≥ 6 months. 6. ECOG performance status ≤ 2. (Patients with lower performance status based solely on
bone pain secondary to MM may be eligible following consultation and approval of the
medical monitor)
7. Patient is a female of childbearing potential (FCBP)* with a negative serum or urine
pregnancy test prior to initiation of therapy and agrees to practice appropriate
methods of birth control, or the patient is male and agrees to practice appropriate
methods of birth control. 8. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent.
9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula
(QTcF) interval of ≤ 470 msec. 10. Renal function: Estimated eGFR by CKD-EPI formula between ≥30 mL/min to <45 mL/min at
screening and at Cycle 1 Day 1 for cohort 1A and 1B, between ≥15 mL/min to < 30 mL/min
for cohort 2A and 2B.
11. The following laboratory results must be met during screening and immediately before
study drug administration on Cycle 1 Day 1:
- - Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors
cannot be used within 10 days [14 days for pegfilgrastim] prior to initiation of
study therapy)
- Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without transfusions during the
10 days prior to initiation of study therapy)
- Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions are permitted)
- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or higher in patients
diagnosed with Gilberts syndrome that have been reviewed and approved by the
medical monitor.
- - AST/SGOT and ALT/SGPT ≤ 3.0 x ULN.
12. Must have, or be willing to have, an acceptable central catheter. (Port a cath,
peripherally inserted central catheter [PICC] line, or central venous catheter)
- - (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or
bilateral oophorectomy or 2) has not been naturally postmenopausal (not having
menstrual cycles due to cancer therapy does not rule out childbearing potential)
for at least 24 consecutive months.
Exclusion Criteria:
1. Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)
2. Evidence of mucosal or internal bleeding and/or platelet transfusion refractory
(platelet count fails to increase by > 10,000 cells/mm3 [10.0 x 109/L] after a
transfusion of an appropriate dose of platelets)
3. Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient or would adversely affect his/her participating in this study.
Examples of such conditions are: a significant history of cardiovascular disease
(e.g., myocardial infarction, significant conduction system abnormalities,
uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months),
4. Known active infection requiring parenteral or oral anti-infective treatment within 14
days of initiation of therapy.
5. Other malignancy diagnosed or requiring treatment within the past 3 years with the
exception of adequately treated basal cell carcinoma, squamous cell skin cancer,
carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in
active surveillance.
6. Pregnant or breast-feeding females. 7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse compliance or follow-up evaluation. 8. Known human immunodeficiency virus or active hepatitis B or C viral infection. 9. Concurrent symptomatic amyloidosis or plasma cell leukemia. 10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein and skin changes)
11. Previous cytotoxic therapies, including cytotoxic investigational agents, for MM
within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of
live vaccines within 30 days before initiation of therapy. IMiDs, PIs and
corticosteroids within 14 days prior to initiation of study therapy. Other
investigational therapies and monoclonal antibodies within 4 weeks of initiation of
study therapy. Prednisone up to but no more than 10 mg orally q.d. or its equivalent
for symptom management of comorbid conditions is permitted but dose should be stable
for at least 7 days prior to initiation of study therapy. Plasmapheresis is not
permitted within 14 days of initiation of therapy.
12. Residual side effects to previous therapy > Grade 1 prior to enrollment (Alopecia any
grade and/or neuropathy Grade 2 without pain are permitted)
13. Prior peripheral stem cell transplant within 12 weeks of initiation of study therapy. 14. Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
15. Prior major surgical procedure or radiation therapy within 4 weeks of the initiation
of study therapy (this does not include limited course of radiation used for
management of bone pain to be completed within 7 days of initiation of study therapy).
16. Known intolerance to steroid therapy. 17. Prior renal transplant. 18. Currently in need of renal dialysis
