Daratumumab, Thalidomide and Dexamethasone in Relapse and/or Refractory Myeloma
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|ClinicalTrials.gov Identifier: NCT03143036|
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : June 7, 2018
Myeloma patients who relapse after prior treatment with bortezomib and lenalidomide have survival of less than 1 year. A number of new drugs have been approved for the treatment of relapse myeloma in the last couple of years, including, Elotuzumab, Panobinostat, Ixazomib, carfilzomib and Pomalidomide. However, most of these drugs either do not have good single agent activity or still belongs to the category of immunomodulatory drugs or proteasome inhibitors. Daratumumab is a monoclonal antibody against CD38 that is highly expressed on myeloma plasma cells. In phase ½ studies, it has impressive single agent activity in relapse and refractory myeloma with a very acceptable toxicity profile. This set the stage for combinations with daratumumab to increase efficacy and improve outcome of patients with myeloma. The use of immunomodulatory drugs, such as thalidomide and lenalidomide, has been shown to augment NK cell activity. NK cells are important mediator of antibody dependent cellular cytotoxicity. We therefore hypothesize that the combination of Daratumumab with thalidomide may therefore improve the efficacy of the treatment.
In this study, we will plan to perform a phase II trial using the Daratumumab, Thalidomide, Dexamethasone combination in 100 myeloma patients with relapse myeloma in Asia.
|Condition or disease||Intervention/treatment||Phase|
|Relapse and / or Refractory Myeloma||Drug: Daratumumab, thalidomide and dexamethasone||Phase 2|
Daratumumab is a humanized antibody against CD38 which is expressed on myeloma cells. Daratumumab exhibited single agent activity in myeloma and is a promising new treatment. Recently, 2 phase 1 / 2 studies establishes the dosing regimen for Daratumumab and impressive single agent activity of about 30% response rates in patients who relapse after prior lenalidomide and bortezomib. Daratumumab also appear to be well tolerated. The most common toxicity is infusion-related and almost all confined to the first cycle. On the whole these are manageable with early intervention, concurrent corticosteroids and anti-histamines as well as slowing infusion rate. More recently, early results from 2 randomise study 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.
In addition, the use of immunomodulatory drugs, such as thalidomide and lenalidomide, has been shown to augment NK cell activity. NK cells are important mediator of antibody dependent cellular cytotoxicity, which is an important mechanism of action for Daratumumab. Furthermore, in the studies using another antibody target SLAMF7, Elotuzumab, the addition of dexamethasone greatly improve efficacy. Furthermore, thalidomide plus dexamethasone combination have a long history in myeloma and is relatively well tolerated and cost-effective. We therefore propose to add Daratumumab to thalidomide and dexamethasone, as this combination will be relatively easy to deliver in the Asian population because of availability and there is good rationale that such a combination will be synergistic and well-tolerated
Patients will be assessed every 28 days (+/-10 days). Patients shall receive the treatment until disease progression, unacceptable toxicity as determined by treating physician, withdrawal of consent or mortality (whichever occurs first). After disease progression, the treating physician should provide long-term follow-up data on disease status and survival. For patients who discontinued treatment before disease progression occurred, disease assessment measurements shall be performed once every 28 days (+/- 10 days) until disease progression. After patients have documented progression of disease, they will be followed for survival every 3 months (+/-10 days) until study closure or until patients withdraws consent, is lost to follow-up or until death, whichever comes first. For any patient who is lost to follow-up, the study site shall attempt to ascertain survival information via public database search.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a phase 2 study of the combination of Daratumumab, thalidomide and dexamethasone in 100 Asian patients with relapse or refractory multiple myeloma.|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Study of Daratumumab in Combination With Thalidomide and Dexamethasone in Relapse and / or Refractory Myeloma|
|Actual Study Start Date :||May 1, 2018|
|Estimated Primary Completion Date :||July 1, 2019|
|Estimated Study Completion Date :||July 1, 2022|
|Experimental: Daratumumab, thalidomide and dexamethasone||
Drug: Daratumumab, thalidomide and dexamethasone
Patients will be treated with with the following schedule. IV daratumumab 16mg/kg body weight weekly for weeks 1-8 followed by daratumumab 16mg/kg body weight once every 2 weeks from weeks 9 to 24 and then daratumumab 16mg/kg once every 4 weeks from weeks 25 onwards until disease progression; PO thalidomide 100mg daily for 1 year and PO Dexamethasone 40mg (starting dose of dexamethasone is 20mg once weekly for patients >75 years old) once weekly for 1 year (13 cycles, each cycle is 4 weeks). After 1 year, patient only continue on daratumumab until progression
Patients will be assessed every 28 days (+/-10 days).
- Progression free survival (PFS) [ Time Frame: Time from commencement of treatment to disease progression or death, whichever occurs first, assessed up to 100 months ]To assess the progression free survival (PFS) for daratumumab in combination with thalidomide and dexamethasone in Asian patients with relapsed myeloma.
- Overall Response Rate (ORR) [ Time Frame: anytime from commencement of treatment with daratumumab, thalidomide and dexamethasone to the end of studyaseline until disease progression, unmanageable adverse event or death, whichever occurs first, approximately up to 3 years ]percentage of patients enrolled that achieve a complete response (CR), or stringent complete response (sCR), or very good partial response (VGPR), or partial response (PR) based on the International Myeloma Working Group criteria
- Overall survival (OS) [ Time Frame: Up to approximately 5 years (anticipated) after the last participant is enrolled ]Time from commencement of treatment with daratumumab, thalidomide and dexamethasone to the date of death.
- Duration of response (DOR) [ Time Frame: the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause, assessed up to 100 months ]the time from first evidence of PR or VGPR, or CR, or sCR to confirmation of disease progression or death due to any cause.
- Number of Participants affected by Adverse Events [ Time Frame: from the time of enrolment into study till 3 years from the date of the last patient randomized ]assessed on the basis of the frequency and severity of adverse events
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): NCT03143036
|Contact: Wee Joo Chng||6779 email@example.com|
|Contact: Adeline Lin||6779 firstname.lastname@example.org|
|Queen Mary Hospital||Not yet recruiting|
|Hong Kong, Hong Kong|
|Korea, Republic of|
|Samsung Medical Center||Not yet recruiting|
|South Korea, Korea, Republic of|
|National University Hospital||Recruiting|
|Singapore General Hospital||Recruiting|
|National Taiwan University||Not yet recruiting|
|Principal Investigator:||Wee Joo Chng||National University Hospital, Singapore|