Clinical trial NCT02419118: "Monoclonal Antibodies for Treatment of Multiple Myeloma. Emphasis on the CD38 Antibody Daratumumab "
Official title: "Monoclonal Antibodies for Treatment of Multiple Myeloma. Present Status and Aspects of Effector Mechanisms With Emphasis on the CD38 Antibody Daratumumab "
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Multiple Myeloma
Keywords: Myeloma
monoclonal antibody
Daratumumab
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2015-04-17
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Daratumumab is a new treatment for patients with myeloma. While many patients benefit from this treatment some do not and the mechanism(s) of failure are poorly understood. This study aims to clarify aspects of resistance to treatment with daratumumab in order to improve patient outcomes in the future.

Detailed description: The effector mechanisms of daratumumab have been extensively studied in vitro, but the in vivo correlates and key determinants of success or failure when daratumumab is used alone or in combination with lenalidomide for treatment of patients with myeloma have not been clarified.

There is potentially a wide spectrum of factors that may influence the quality and duration of response following treatment with daratumumab. The integrity of the patient's immune system may be important. Prior lines of chemotherapy or the myeloma disease itself may impair humural (i.e. complement) or cellular (i.e. ADCC) effector mechanisms that are of importance for the response to daratumumab. Also intrinsic properties of the tumor cells or interactions between myeloma cells and the bone marrow microenvironment could make the myeloma cells refractory to daratumumab.

A better understanding of these variables may enable us to improve the quality and duration of daratumumab-induced responses and make daratumumab-based therapies more effective in the near future.

Eligibility criteria: Inclusion Criteria:

* Accepted for a clinical trial with Daratumumab for myeloma

Exclusion Criteria:

* None

Primary outcomes:
measure: Response by IMWG criteria
timeFrame: 4 weeks
Secondary outcomes:
measure: T cell subset numbers
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Department of Hematology Vejle Hospital
Study officials:
affiliation: Vejle Hospital
name: Torben Plesner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Franssen LE, van de Donk NW, Emmelot ME, Roeven MW, Schaap N, Dolstra H, Hobo W, Lokhorst HM, Mutis T. The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. Bone Marrow Transplant. 2015 Jun;50(6):822-8. doi: 10.1038/bmt.2015.48. Epub 2015 Mar 23.
citation: Overdijk MB, Verploegen S, Bogels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, Groen RW, Breij E, Martens AC, Bleeker WK, Parren PW. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7(2):311-21. doi: 10.1080/19420862.2015.1007813.