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

Intergroupe Francophone du Myelome1,085 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,085

Conditions

Multiple Myeloma

Interventions

Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD)DRUG

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

Bortezomib, Thalidomide, Dexamethasone (VTD) + daratumumabDRUG

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

DaratumumabDRUG

Daratumumab 16mg/kg every 8 weeks for 2 years

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (107)

Outcomes

Primary Outcomes

Post-Consolidation Stringent Complete Response (sCR) Rate

Post-consolidation sCR rate is defined as the percentage of ITT subjects who achieved or maintained sCR status within 30 days of Day 100 post Autologous Stem Cell Transplant (ASCT). The sCR status is assessed using the computerized algorithm according to IMWG response criteria, and must be achieved on or prior to start of subsequent therapies. Subjects must not die or progress by Day 100 post ASCT. According to the IMWG consensus recommendations for multiple myeloma treatment response criteria from 2006, the stringent complete response (sCR) was defined by a negative immunofixation on the serum and urine, and a disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow, plus normal free-light chain ratio and the absence of clonal bone marrow plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

Time frame: At day 100 post Autologous Stem Cell Transplant (ASCT), up to 114 days post ASCT

Progression Free Survival (PFS) Post Completion of Maintenance Therapy

Progression Free Survival (PFS) post completion of maintenance therapy is defined as the duration from the date of second randomization to either progressive disease (according to the IMWG criteria specified in the protocol), or death, whichever occurs first (=all these considered as events) at the completion of Maintenance therapy.

Time frame: From the date of second randomization to either progressive disease or death which ever occurred first, with a median follow-up time of 35.4 months (cut-off for analysis was 26 months after the last rando 2 date).

Secondary Outcomes

Progression Free Survival (PFS) From First Randomization up to the End of the Study

Progression Free Survival (PFS) is defined as the duration from the date of first randomization to either progressive disease (according to the IMWG criteria specified in the protocol), or death, whichever occurs first (=all these considered as events) at the end of the study

Time frame: From the date of first randomization to either progressive disease or death which ever occurred first, with a median follow-up time of 80.1 months at the end of the study

Data from ClinicalTrials.gov

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