A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if the addition of daratumumab to Bortezomib, Thalidomide and Dexamethasone will increase the stringent complete response rate after consolidation therapy and increase the progression free survival after daratumumab maintenance therapy in transplant eligible participants with previously untreated Multiple Myeloma.

Detailed Description
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This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 2-arm (2 treatment groups), multicenter study of daratumumab in participants diagnosed with previously untreated Multiple Myeloma who are eligible for high dose chemotherapy and autologous stem cell transplantation (transplantation of own bone marrow). Participants will be randomized (assigned by chance) to one of 2 treatment groups to either receive daratumumab plus bortezomib, thalidomide and dexamethasone or bortezomib, thalidomide and dexamethasone for induction (before transplantation) and consolidation (after transplantation) treatment. All responders will then be re-randomized (assigned by chance) to one of 2 treatment groups to receive maintenance treatment with daratumumab only or observation (no treatment). The study will include a 28-Day Screening Phase, a Treatment Phase of 6 treatment cycles (each cycle is 4 weeks in duration for total period of 30 weeks), and a Follow up Phase of 2 years. The total duration for each participant in the study will be approximately 138 weeks. The end of the study will occur approximately 5 years after the last participant is randomized in the second phase of the study. Disease assessments will be performed every 4 weeks in the first phase of the study and then every 8 weeks in the second phase of the study. Safety will be monitored throughout the study.

Official Title
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Study of Daratumumab in Combination With Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) in the First Line Treatment of Transplant Eligible Subjects With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)
* Drug: Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab
* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of previously untreated multiple myeloma (MM) Have a confirmed diagnosis and eligible for high dose chemotherapy and autologous stem cell transplantation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1 or 2 Exclusion Criteria: previous treatment for Multiple Myeloma Primary amyloidosis, Plasma Cell Leukemia or Smoldering Multiple Myeloma Prior or concurrent exposure to systemic therapy or SCT (Stem Cell Transplantation) for any plasma cell dyscrasia, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment, or received an investigational drug or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1 history of malignancy (other than Multiple Myeloma) within 10 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix known chronic obstructive pulmonary disease (COPD) or moderate to severe asthma any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A Part 1<br>Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) | Drug: Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)<br>* Part 1: 4 Cycles of Bortezomib,Thalidomide and Dexamethasone induction therapy, followed by Autologous Stem Cell Transplantation, followed by 2 cycles of Bortezomib, Thalidomide and Dexamethasone consolidation<br>* Other names: Arm A Part 1;|
| Experimental: Arm B Part 1<br>Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) plus daratumumab | Drug: Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumab<br>* Part 1: 4 Cycles of Bortezomib, Thalidomide and Dexamethasone plus daratumumab 16mg/kg induction therapy, followed by Autologous Stem Cell Transplantation, followed by 2 cycles of Bortezomib, Thalidomide and Dexamethasone plus daratumumab 16 mg/kg consolidation<br>* Other names: Arm B Part 1;|
| No Intervention: Arm A Part 2<br>Observation | |
| Experimental: Arm B Part 2<br>daratumumab | Drug: Daratumumab<br>* Daratumumab 16mg/kg every 8 weeks for 2 years<br>* Other names: Arm B Part 2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stringent complete response (sCR) after consolidation therapy | sCR is defined by achieving CR (complete response) in addition to having a normal serum FLC (Free Light Chain) ratio and absence of clonal cells in bone marrow | Up to 9 months | 
| Progression free survival after maintenance therapy | Time from the date of second randomization to either progressive disease (PD) or death | up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (Progression-Free Survival) (from first randomization) | time from the initial randomization to either confirmed progressive disease (PD) or death | Up to 60 months | 
| Time to Progression (TTP) | Time from the initial randomization to confirmed progressive disease (PD) or death due to progressive disease | Up to 60 months | 
| proportion of Post ASCT (Autologous Stem Cell Transplantation) / consolidation CR rate | Proportion of participants who have achieved CR or sCR by the end of consolidation treatment | Up to 9 months | 
| proportion of Post ASCT/consolidation MRD (Minimal Residual Disease) negativation | proportion of participants who have achieved MRD (minimal residual disease) negative status by the end of consolidation | Up to 9 months | 
| proportion of Post induction sCR | proportion of participants who have achieved sCR (stringent complete response) prior to high-dose therapy/ASCT (autologous stem cell transplantation) | Up to 4 months | 
| PFS 2 (from first randomization) | time from initial randomization to subsequent progression on next-line of therapy after disease progression on study treatment | Up to 60 months | 
| OS (overall survival) (from first randomization) | time from initial randomization to death | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Untreated Multiple Myeloma, daratumumab