Autologous Stem Cell Transplantation, Multiple Myeloma, Newly Diagnosed Multiple Myeloma
Conditions
Keywords
Daratumumab, lenalidomide, bortezomib, dexamethasone
Brief summary
This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in subjects with newly diagnosed multiple myeloma (NDMM) who are eligible for standard-of-care autologous stem cell transplantation (ASCT). Daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) have recently become a standard induction regimen for patients with NDMM who are eligible for ASCT in the United States. As implemented in clinical trials, Dara-RVd involves twice weekly bortezomib administration, which is inconvenient for patients and may result in increased rates of limiting toxicity, such as peripheral neuropathy. Adoption of alternate schedules involving once-weekly bortezomib is common in real-world practice, however a paucity of prospective data supporting this practice exists. This study examines the efficacy of an attenuated Dara-RVd schedule involving once-weekly bortezomib dosing.
Interventions
BIOLOGICALDaratumumab
Daratumumab is a CD38-directed cytolytic antibody indicated for the treatment of adults with multiple myeloma. 1800 mg will be given subcutaneously according to its standard package insert schedule.
DRUGLenalidomide
Lenalidomide will be administered, once daily orally on Days 1-21 of a 28-day
DRUGBortezomib
Bortezomib is a proteasome inhibitor indicated for the treatment of adult patients with multiple myeloma, will be given subcutaneously once weekly on days 1, 8, and 15 of every 28 day cycle.
DRUGDexamethasone
Dexamethasone is a glucocorticoid.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator. 2. Age ≥18 years at the time of consent. 3. Eastern Cooperative Oncology Group (ECOG) ≤ 2 4. Subjects with Multiple Myeloma.
Exclusion criteria
1. Active infection requiring systemic therapy or other serious infection within 14 days prior to study treatment. 2. Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The rate of achievement of bone marrow minimal residual disease (MRD) negativity | At completion of stem cell transplantation (60 days) | The rate of achievement of bone marrow minimal residual disease (MRD) negativity will be defined as the percentage of subjects achieving MRD negativity as determined by next-generation flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS ) | Up to 2 years | PFS will be defined as the time from the start of study treatment until progression per revised Uniform Response Criteria by the International Myeloma Working Group (IMWG) or death from any cause. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
| Stringent complete response (sCR) | At completion of stem cell transplantation (60 days) | Stringent complete response (sCR) will be defined according to the standard International Myeloma Working Group (IMWG) response criteria for multiple myeloma. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
| Overall Survival (OS) | Up to 2 years | OS will be defined as the time from the start of treatment to death from any cause. |
| Therapeutic discontinuation | Up to 2 years | Therapeutic discontinuation will be defined as a treatment discontinuation of all drugs for any reason. |
| Time to first response | Up to 2 years | Time to first response will be defined as time from the start of study treatment until the first achievement of at least a partial response (PR) by IMWG criteria or better. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
| Time to best response | Up to 2 years | The time to best response will be defined as the time from the start of study treatment until the time at which a patient's best response according to IMWG criteria is achieved. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
| Maximum depth of response (from PR to CR, including sCR) | Up to 2 years | The maximum depth of response (from PR to CR, including sCR) will be determined based on IMWG criteria. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
| Overall response rate (ORR) | Up to 2 years | ORR will be defined as the percentage of subjects achieving a partial response (PR) or better according to IMWG criteria. Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSamuel M Rubinstein, MD, MSCI
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed