Clinical Trial 19230

Cancer Type: Malignant Hematology
Interventions:Bortezomib; CC-5013 (Lenalidomide); Daratumumab; Dexamethasone; Lenalidomide (Revlimid); PS-341 (Bortezomib); Velcade (Bortezomib)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Kenneth Shain

Overview

Study Title

Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib,and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy and Autologous Stem Cell Transplantation

Summary

This research study for participants with newly diagnosed Multiple Myeloma is looking at the safety and effectiveness of a study drug, Daratumumab, when added to a standard of care treatment, Revlimid® (lenalidomide), Velcade® (bortezomib), and dexamethasone (RVd) alone.

Objective

Primary Objective: The primary objective is to determine if the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) will increase the proportion of subjects achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post-autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone. Secondary Objectives: To evaluate complete response (CR) and sCR rate following induction, ASCT, post-ASCT consolidation, and maintenance treatment. To evaluate overall response rate (ORR) and rate of very good partial response (VGPR) or better following induction, ASCT, post-ASCT consolidation, and maintenance treatment. To evaluate duration of and time to sCR and time to CR. To evaluate time to VGPR or better. To evaluate time to partial response (PR) or better. To assess negative minimal residual disease (MRD) rate following induction, ASCT, post-ASCT.consolidation, and maintenance treatment. To evaluate clinical outcomes including: Time to progression (TTP); Progression-free survival (PFS); Overall survival (OS); Duration of response. To assess the safety and tolerability of D-RVd. To assess the pharmacokinetics of daratumumab. To assess the immunogenicity of daratumumab JNJ-54767414 (daratumumab) To evaluate patient-reported outcomes (PROs). To evaluate stem cell yield after mobilization. To assess time to engraftment, defined as absolute neutrophil count >1.0 x 10^9/L and platelet count >100 x 10^9/L. Exploratory Objectives: To evaluate PFS on next-line therapy. To evaluate the clinical efficacy of D-RVd in high-risk cytogenetic subgroups: del(1p), gain of 1q, del(17p), t(4;14), t(14;16), t(14;20). To explore immune modulatory effects of D-RVd as compared with RVd through immune profiling (NK, T, and B cells) and T-cell receptor sequencing. To collect medical resource utilization (MRU) data that may be used in future economic modeling (the construction and reporting of the economic model will be conducted separately from this study).

Inclusion Criteria

  • Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
  • Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose

  • Exclusion Criteria

  • Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (e.g.., cervical, breast) with no evidence of disease.
  • Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
  • Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (> Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
  • Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study.