ATRA and Carfilzomib in Plasma Cell Myeloma Patients

Inclusion Criteria:

1. Age ≥ 18 years with relapsed/refractory multiple myeloma documented according toInternational Myeloma Working Group (IMWG) criteria.

2. Previously treated with at least three lines of therapy which would includeImmunomodulatory drugs (IMiDs), Proteosome inhibitors (including carfilzomib),anti-CD 38 antibodies and failed to achieve a minor response after completing atleast 2 cycles of carfilzomib-based therapy or are relapsed while on therapy.

3. Patient or legal guardian voluntarily can sign informed consent.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2

5. Adequate organ function defined as:

6. Hemoglobin ≥8 g/dL (baseline or after Peripheral Red Blood Cell transfusion),Platelet count >75,000 and Absolute Neutrophil Count >1000/ micro liter.

7. Left Ventricular Ejection fraction ≥50%

8. Creatinine Clearance ≥ 30 ml/min

9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upperlimit of normal (ULN)

10. Total bilirubin ≤ 1.5 × ULN

11. Measurable disease requiring treatment defined as patients having one or more of thecriteria below:

12. Serum M protein ≥ 0.5 g/dL or

13. Urine M-protein ≥ 200 mg/24 hours or

14. Serum free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormalserum

15. kappa lambda ratio.

16. If previous autologous stem cell transplantation, must have fully recovered fromtransplant related toxicities and be >60 days from transplant and have hadhematologic recovery independent of growth factor support.

17. Willingness to undergo interim bone marrow biopsy as scheduled or if felt to bemedically indicated.

18. Life Expectancy ≥ 6 months

19. Women with childbearing potential and men should practice at least one of thefollowing methods of birth control:

20. Total abstinence from sexual intercourse (periodic abstinence not acceptable);

21. Surgically sterile partner(s) including vasectomy, bilateral tubal ligation,bilateral oophorectomy, or hysterectomy;

22. Intrauterine device with an additional method of contraception to make twoeffective methods of contraception during treatment with Vesanoid;

23. Double-barrier method (condom + diaphragm or cervical cap with spermicide,contraceptive sponge, jellies, or cream);

24. Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) for atleast 3 months prior to study drug administration. If hormonal contraceptivesare used, the specific contraceptive must have been used for at least 3 monthsprior to study drug administration. If the patient is currently using ahormonal contraceptive, she should also use a barrier method during this studyWomen of child-bearing potential must have a negative results of a pregnancytest performed at initial screening on a serum sample obtained within 21 daysprior to C1D1, and prior to dosing on a urine sample obtained within 72 hoursof the first study drug administration. Males must refrain from sperm donationsfrom date of C1D1 to 90 days after the last date of the study drug.

Exclusion Criteria:

1. Non-secretory or hyposecretory multiple myeloma, defined as <0.5 g/dL M-protein inserum, <200 mg/24-hour urine M-protein, or disease only measured by serum free lightchain.

2. Plasma Cell Leukemia (Previously treated Plasma Cell Leukemia can be included per PIdiscretion)

3. Concurrent light chain amyloidosis

4. Central nervous system involvement (patients with known brain metastases have poorprognosis and often develop progressive neurologic dysfunction that may confound theevaluation of neurologic and other Adverse Events while on ATRA).

5. Pregnant or breast feeding

6. Severe, active, recurrent, or intercurrent infection (viral, bacterial, fungal), ordiagnosis of neutropenia and fever within one week of C1D1.

7. History of Allogeneic hematopoietic cell transplantation or solid organtransplantation.

8. Unstable angina pectoris, cardiac arrhythmia or > New York Heart Failure associationclass II cardiac failure, defined as comfortable at rest but ordinary physicalactivity results in fatigue, palpitations, dyspnea, or anginal pain.

9. Patient has a significant history of renal, neurologic (peripheral neuropathy),psychiatric, endocrinologic (diabetes mellitus), metabolic, immunologic,cardiovascular, pulmonary, hepatic disease, or significant social situation withinthe past 6 months that, in the opinion of the investigator, would impede his/herability to fully participate in the study. For patients who have required anintervention for the above diseases within the past 6 months, a case-by-casediscussion with the investigator must occur.

10. On investigational therapies within 12 weeks of enrollment.

11. Previous allergic reaction or intolerance to a proteasome inhibitor, includingcarfilzomib, bortezomib, or ixazomib.

12. Or deemed unfit for the study on evaluation by Investigator.