Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) With Daratumumab (DARA) (CyBorD-Dara)
This study is a Phase Ib open label, single arm, adaptive multicentre trial. Patients with newly diagnosed Multiple Myeloma (MM) will be treated with Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) in combination with Daratumumab (DARA).
The safety profile of daratumumab to date, which does not appear to overlap with those known for approved agents, combined with its distinct MoA, suggest that the therapeutic profile of daratumumab combined with various backbone regimens may improve the treatment effect of these regimens. Additionally, daratumumab as a single agent may prolong the progression free interval for these patients. Based on the potential for cyclophosphamide to enhance ADCP, there is a strong rationale to combine DARA with a cyclophosphamide, bortezomib containing regimen. This will be the first clinical trial to explore the feasibility of combining daratumumab with a cyclophosphamide containing backbone induction regimen and if successful will provide the rationale for larger studies exploring the efficacy of this combination in greater detail.
|Multiple Myeloma||Drug: Daratumumab Drug: Cyclophosphamide Drug: Bortezomib Drug: Dexamethasone||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase Ib Study of Weekly Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) With Daratumumab (DARA) in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma (MM): "The CyBorD-DARA Study"|
- MTD [ Time Frame: 15 months ]To determine the Maximum Tolerated Dose (MTD) for cyclophosphamide and bortezomib that can be safely administered with DARA.
- The rate of Complete Response (CR) post Autologous Stem Cell Transplantation (ASCT) [ Time Frame: 42 months ]Efficacy assessed by the rate of Complete Response (CR) post Autologous Stem Cell Transplantation (ASCT)
- Safety and Tolerability as assessed by adverse events [ Time Frame: 42 months ]Safety and Tolerability will be assessed by standard clinical and laboratory tests. Adverse event grades will be determined by the NCI CTCAE v4.03
- Complete Response Rate at the end of induction, ASCT, consolidation and maintenance [ Time Frame: 42 months ]
- Best Overall Response [ Time Frame: 42 months ]
- Minimal Residual Disease (MRD) negative rate at the end of induction, ASCT, consolidation and maintenance [ Time Frame: 42 months ]
- Progression Free Survival (PFS) at the end of maintenance phase [ Time Frame: 42 months ]
- Overall Survival (OS) at the end of maintenance phase [ Time Frame: 42 months ]
- Clinical Benefit Rate (CBR) [ Time Frame: 42 months ]
|Study Start Date:||November 2016|
|Estimated Study Completion Date:||November 2020|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
The study will consist of 2 phases:
- The Screening Phase will extend up to 28 days prior to Cycle 1, Day 1.
- The Treatment Phase will be conducted in 2 parts and will extend from Cycle 1 Day 1 until treatment discontinuation.
Treatment Phase, Part 1: Induction/Transplantation/Consolidation Phase. The consolidation phase of treatment will begin approximately 30-60 days after Autologous Stem Cell Transplantation (ASCT), when the patient has recovered sufficiently and engraftment is complete.
Treatment Phase, Part 2: Maintenance Phase treatment until a maximum duration of 2 years, documented disease progression, death, loss to follow-up, or withdrawal of consent, whichever occurs first.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02955810
|Contact: Amanda Bray||+353(0)91 49 firstname.lastname@example.org|
|Galway University Hospital||Recruiting|
|Contact: Amanda Bray +353(0)87 628 6562 email@example.com|
|Contact: Roisin Costello firstname.lastname@example.org|
|Principal Investigator: Michael O'Dwyer, MD|