Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03695744|
Recruitment Status : Not yet recruiting
First Posted : October 4, 2018
Last Update Posted : October 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma Myeloma||Drug: Daratumumab Drug: Bortezomib Drug: Dexamethasone||Phase 2|
Newly diagnosed Multiple Myeloma patients who ineligible for a transplant have inferior outcomes compared to that of the transplant population. This is an area of high unmet need and calls for newer therapies with novel mechanisms of action to better improve survival in this non-transplant eligible (NTE) group. Currently NTE patients will be treated with a Bortezomib based or Lenalidomide based doublet or triplet regimen as first-line.
Daratumumab is a monoclonal antibody that targets CD38 expressed at high levels on myeloma plasma cells. In phase 1/2 studies, it has demonstrated impressive single agent activity in relapse and refractory myeloma with a very acceptable toxicity profile and is a promising new treatment. This set the stage for combinations with daratumumab to increase efficacy and improve outcomes of patients in both the relapse refractory and newly diagnosed settings. Addition of daratumumab to any number of the backbone regimes have been shown to be of good efficacy. 2 phase 1 / 2 studies established the dosing regimen for Daratumumab as a single agent in patients who relapse after prior lenalidomide and bortezomib.
More recently, results from 2 randomised studies comparing Daratumumab plus lenalidomide and dexamethasone compared to lenalidomide and dexamethasone, and Daratumumab plus bortezomib and dexamethasone compared to bortezomib and dexamethasone, showed that the addition of Daratumumab significantly improved response and progression free survival, including a high minimal residual disease (MRD) negative rate of more than 20% in the relapse myeloma populations.
Another recent study showed that a different 4 drug combination of Daratumumab, bortezomib and Melphalan and Prednisolone in the front line setting of non-transplant Myeloma had promising response rates and was a quite tolerable combination.
All the above Daratumumab trials demostrated that deeper responses are achieved by antibody - Proteasome inhibitor or Antibody - ImiD combinations. It is known that deeper response in myeloma are associated with longer progression free and overall survival. Hence this trial using the three drug combination of Daratumumab, Bortezomib and Dexamethasone is proposed to explore its efficacy by demonstarting an improvement in overall response rates, complete response rates and to document its safety/tolerability in our population.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||AMN006 - Phase 2 Study of Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients|
|Estimated Study Start Date :||October 2018|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||October 2023|
Experimental: Daratumumab Bortezomib Dexamethasone
IV daratumumab 16mg/kg body weight weekly for weeks 1-9 followed by daratumumab 16mg/kg body weight once every 3 weeks from weeks 10 to 24 and then daratumumab 16mg/kg once every 4 weeks from weeks 25 onwards until disease progression; S.C bortezomib and PO Dexamethasone 40mg (starting dose of dexamethasone is 20mg once weekly for patients >75 years old) once weekly for 9 months from start of study. After 9 months, patient only continues on daratumumab until progression.
- Overall Response [ Time Frame: From the date of treatment commencement till the date of best response as per IMWG definitions, upto 3 years ]Number of patients achieving responses as defined by the IMWG Criteria
- PFS [ Time Frame: From date of commencement of trial treatment until the date of first documented progression or date of death from any cause, whichever occurs first assessed upto 100 months ]Progression Free Survival
- OS [ Time Frame: From commencement of trial treatment to death from any cause assessed upto 100 months ]Overall Survival
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03695744
|Contact: Chandramouli Nagarajan, MD FRCPathemail@example.com|
|Contact: Ee Mei Tehfirstname.lastname@example.org|
|Singapore General Hospital|