NCT02626481

Study of Daratumumab in Combination With Dexamethasone in Resistant or Refractory Multiple Myeloma

A Multicenter Open Label Phase II Study of Daratumumab in Combination With Dexamethasone in Multiple Myeloma Resistant or Refractory to Bortezomib and Lenalidomide and Pomalidomide - an IFM 2014-04 Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: University Hospital, Lille · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a Multicentre, Open-label, Phase II study of Daratumumab and Dexamethasone in MM patients. Eligible patients must have a symptomatic RRMM with a measurable disease, resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide. There is no dose escalation phase, as the MAxiamal Tolerated Dose (MTD) and drug scheduling have already been determined in previous phase 1-2 dose escalation studies. There is no randomization.

Detailed description

Multiple myeloma (MM) is the second most common haematological malignancy (after non-Hodgkin's lymphoma), representing 1% of all cancers and 2% of all cancer deaths. Despite the increased efficacy of first-line agents, the majority of patients will eventually relapse and become resistant to all classes of available therapies. With over 15,000 deaths from MM expected in 2014 in the United states of America (USA) alone, there remains a need for novel therapies for the treatment of refractory MM that can improve outcome Daratumumab is an IgG1ĸ human mAb that specifically recognizes the CD38 epitope. Daratumumab binds to the C-terminus of CD38. It is produced in a recombinant Chinese Hamster Ovary (CHO) cell line. Standard mammalian cell culture and purification technologies are employed in the manufacture of Daratumumab. Daratumumab targets directly the tumour cells by selectively binding to CD38 receptors, present in high levels on malignant plasma cells in multiple myeloma. While binding of Daratumumab antibody to CD38 in vitro has some effect on enzyme activity (inhibiting cyclase and stimulating hydrolase activity), the main effect of Daratumumab antibody binding to CD38+ myeloma cell lines is lysis and cell death through complement dependent cytotoxicity (CDC), through antibody dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell phagocytosis (ADCP), or by direct apoptosis following crosslinking of the antibody molecules. These mechanisms are likely to be involved in Daratumumab activity in vivo, although the primary mechanism of action in patients is not fully elucidated. Importantly, Daratumumab-induced ADCC and CDC was not affected by the presence of bone marrow stromal cells, indicating that Daratumumab can effectively kill MM tumour cells in a tumour-preserving bone marrow microenvironment. In vivo, Daratumumab was highly active and interrupted xenograft tumour growth at low dosing. Daratumumab has demonstrated activity in myeloma as a single agent in small phase I/II studies and in combination with Lenalidomide and Dexamethasone where it enhanced the potency of other MM drugs such as Lenalidomide offering an interesting alternative to chemotherapy in myeloma.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Daratumumab	patients treated with Daratumumab (16 mg/kg) and Dexamethasone (40 or 20 mg regarding age of patient)
DRUG	Dexamethasone	patients treated with Dexamethasone (40 or 20 mg regarding age of patient)

Timeline

• Start date: 2015-12-28
• Primary completion: 2020-03-09
• Completion: 2020-03-09
• First posted: 2015-12-10
• Last updated: 2026-04-07

Locations

41 sites across 2 countries: Belgium, France