NCT03184194

Nivolumab Combined With Daratumumab With or Without Low-dose Cyclophosphamide

A Phase 2 Study of Nivolumab Combined With Daratumumab With or Without Low-dose Cyclophosphamide in Relapsed/Refractory Multiple Myeloma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Evaluation of the effect of nivolumab and daratumumab with or without low-dose cyclophosphamide in patients with relapsed/refractory multiple myeloma.

Detailed description

Myeloma patients who develop bortezomib and lenalidomide-resistant disease have a very poor survival of only a median of 9 months, indicating that new agents are urgently needed. Recent studies have shown that daratumumab as a single agent is effective and well tolerated in these heavily pretreated MM patients. However, approximately 60% of patients do not achieve a partial response, and ultimately all patients will develop progressive disease during daratumumab therapy. In less pretreated patients daratumumab-based combinations (daratumumab plus lenalidomide-dexamethasone or daratumumab plus bortezomib-dexamethasone) were very effective and well tolerated. Therefore, in this study, the investigators will combine daratumumab with other agents to improve survival of heavily pretreated MM patients. The PD-1 blocker nivolumab, as single agent, does not induce objective responses but induces stable disease in approximately 67% of relapsed/refractory MM patients. We have recently shown that daratumumab treatment results in increased T cell frequencies by eliminating CD38-positive immune suppressor cells, which probably contributes to the durable responses observed with daratumumab. Cyclophosphamide, at a dose substantially lower than the maximum tolerated dose, has next to its direct anti-tumor activity serveral other effects including anti-angiogenic effects, induction of changes in the micro-environment, and also improvement of the anti-tumor immune response. In this study, the investigators will combine two or three immune modulating agents with different mechanisms of action in order to improve the outcome of relapsed/refractory MM patients. The investigators will evaluate in Part A, nivolumab combined with daratumumab with or without low-dose cyclophosphamide (total 40 patients). Based on efficacy and tolerability, the investigators will treat in Part B 20 additional patients with nivolumab combined with daratumumab either with or without low-dose cyclophosphamide based on tolerability and efficacy data obtained in Part A.

Conditions

• Myeloma

Interventions

Type	Name	Description
DRUG	nivolumab-daratumumab	nivolumab-daratumumab will be given without low-dose cyclophosphamide until progression
DRUG	nivolumab-daratumumab with low-dose cyclophosphamide	nivolumab-daratumumab with low-dose cyclophosphamide will be given until progression

Timeline

• Start date: 2018-02-21
• Primary completion: 2023-01-25
• Completion: 2024-01-25
• First posted: 2017-06-12
• Last updated: 2024-05-22

Locations

9 sites across 1 country: Netherlands