Ignite Creation Date:
2025-12-25 @ 1:38 AM
Ignite Modification Date:
2026-01-07 @ 1:57 AM
Study NCT ID:
NCT03184194
Status:
COMPLETED
Last Update Posted:
2024-05-22
First Post:
2017-06-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Nivolumab Combined With Daratumumab With or Without Low-dose Cyclophosphamide
Sponsor:
Amsterdam UMC, location VUmc
Organization:
Study Overview
Official Title:
A Phase 2 Study of Nivolumab Combined With Daratumumab With or Without Low-dose Cyclophosphamide in Relapsed/Refractory Multiple Myeloma
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: