This study is conducted in two parts. In part I, subjects are enrolled into cohorts at increasing dose levels. Subject safety and efficacy during part I will determine the doses used for Part II. In Part II subjects will be enrolled into one treatment arm; Maximal Tolerated Dose as defined in part I.

Both Part I and Part II are open-label/unmasked.

Inclusion criteria

1. Diagnosis of MM requiring systemic therapy
2. Age ≥ 18 years
3. ECOG performance status (0-2)
4. Life expectancy > 3 months
5. Relapsed or refractory to two or more different prior therapies
6. Signed Informed consent

Exclusion criteria

1. Plasma cell leukemia
2. Known amyloidosis
3. Patients who previously have received an allogeneic stem cell transplant and receive or have received immunosuppressive therapy within the last three months

   or

   Patients who previously have received an allogeneic stem cell transplant and have signs of acute or chronic graft-versus-host disease

4. Sensory or motor neuropathy ≥ grade 3
5. Past or current malignancy
6. Chronic or ongoing active infectious disease
7. Clinically significant cardiac disease
8. Significant concurrent, uncontrolled medical condition including, but not limited to, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
9. A baseline QT interval as corrected by Fridericia's formula > 470 msec for female patients or > 450 msec for male patients or a complete left bundle branch block (defined as a QRS interval≥ 120 msec in left bundle branch block form)
10. Hypokalemia
11. Clinical signs of meningeal involvement of MM
12. Known severe chronic obstructive pulmonary disease or asthma defined as FEV1< 60% of expected
13. History of significant cerebrovascular disease
14. Known Human Immunodeficiency Virus seropositivity
15. Positive serology for hepatitis B
16. Screening laboratory values
17. Concomitant corticosteroid
18. Other chemotherapy that is or may be active against myeloma within 3 weeks prior to Visit 1 (Part 2)
19. Known hypersensitivity to components of the investigational product or severe allergic or anaphylactic reactions to humanized products
20. Patients who have received treatment with any nonmarket drug substance within 4 weeks before Screening (Part 1: Visit 1; Part 2: Visit 0)
21. Current participation in any other interventional clinical trial
22. Patients known or suspected of not being able to comply with a trial protocol (eg, due to alcoholism, drug dependency, or psychological disorder)
23. Breastfeeding women or women with a positive pregnancy test at Screening
24. Women of childbearing potential not willing to use adequate contraception, defined as hormonal birth control or intrauterine device, during the trial and for 1 year after the last dose of daratumumab. For patients in the US, the use of a double-barrier method is also considered adequate