Newly diagnosed multiple myeloma Cancer Multiple myeloma and malignant plasma cell neoplasms
Conditions
Interventions
A randomised phase III trial has been chosen in order to compare the difference in the proportion of patients who achieve myeloma cell negativity in their day 100 post-transplant bone aspirate and oth
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Confirmed diagnosis of symptomatic MM, both those with; measurable secretory disease according to IMWG criteria and patients with non-secretory myeloma may enter the trial 2. Received only 1st line induction therapy (i.e., undergoing or completed first line therapy at the time of enrolment)* 3. Induction with either VCD or VTD** 4. Received Bortezomib-containing induction treatment for at least 4 cycles 5. Achieving at least PR following induction treatment 6. Considered suitable for ASCT at the time of entering the trial as clinically judged by the local Investigator 7. ECOG =18 9. Creatinine clearance >=30ml/min 10. Adults of reproductive potential must agree to use effective contraception or maintain abstinence for 6 months after therapy 11. Willing and able to participate in all required evaluations and procedures in this study *This trial will adopt the general definitions for a cycle of chemotherapy, whereby a line of therapy consists of >=1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens (e.g., 3 - 6 cycles of initial therapy with bortezomib-dexamethasone (VD) followed by stem cell transplantation (SCT), consolidation, and lenalidomide maintenance is considered 1 line). However, since standard practice in many UK centres includes an adaptive approach whereby VCD or VTD is started, but a swap to VTD or VCD respectively is planned depending on response and tolerability, these two combinations (i.e. VCD changing to VTD or VTD changing to VCD) will be considered a single line of therapy and patients will be eligible for this trial. **This study will recruit patients who have received either VCD or VTD induction therapy. However, since standard practice in many UK centres includes switching from one regimen to the other, we will therefore allow enrollment into the study of patients who have swapped from VCD to VTD or from VTD to VCD.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with daratumumab or other anti-CD38 therapies 2. Demonstrating evidence of progressive disease according to IMWG criteria 3. Peripheral neuropathy above grade 2 as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 4. Current or prior malignancy within 5 years from enrolment (other than multiple myeloma, adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or prostate cancer 2 x upper limit of normal (ULN) 6. ALT/AST >3 x ULN 7. Known chronic obstructive pulmonary disease (COPD), persistent asthma or pulmonary function tests showing Forced Expiratory Volume (FEV1) <60% 8. Known cardiac impairment with Left Ventricular Ejection Fraction (LVEF) <50% 9. Pregnant or breast-feeding women. (Women of child-bearing potential and men who are sexually active will be required to undergo the standard testing prior to chemotherapy, which we will not list here for brevity.) 10. POEMS syndrome, plasma cell leukaemia, amyloidosis (AL), smouldering multiple myeloma, Waldenstrom's macroglobulinaemia. 11. Known or suspected central nervous system (CNS) involvement by myeloma 12. Radiation therapy within 4 weeks of trial entry 13. Participation in an investigational therapeutic study within the 4 weeks prior to first dose of daratumumab 14. Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to trial entry 15. Known or suspected human immunodeficiency virus (HIV) infection or subjects who are HIV seropositive 16. Active hepatitis A, B (surface antigen or core antibody positive), or C infection (patients with no detectable virus by PCR may be entered into the study with ongoing monitoring and therapy for viral reactivation as per local practice) 17. Serious psychiatric or medical conditions that could, in the investigator’s opinion, interfere with treatment, protocol adherence or a subject's ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients with MRD-negative bone marrow aspirate (defined as malignant plasma cells <1 in 10(5) total cells) measured by multiparameter flow cytometry at day 100 after autologous stem cell transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and toxicity of addition of daratumumab to PBSC harvest and ASCT: 1. Rate of graft failure - measured by blood sample – time point within 28 days of stem cell transplant 2. Time to engraftment - measured by blood sample – time point within 28 days of stem cell transplant 3. Proportion of patients completing treatment as per protocol – measured by review of patient data – time point at day 100 after stem cell transplant 4. Proportion of patients achieving a stem cell harvest yield of =4 x 10 to the 6 CD34+ cells/kg – measured by number of cells collected in stem cell harvest and review of patient data were the number of cells is recorded – time point day 10 of the mobilisation and collection phase of the stem cell transplant 5. Toxicity collected accordance with CTCAE criteria 5.0 - measured by review of adverse events collected in the patients records - time point up to day 100 after the admission of the last treatment/transplant 6. Proportion of patients achieving a = 10 fold reduction in disease burden - measured by multiparameter flow cytometry of bone marrow samples and review of patient data were results will be recorded comparing - time point pre-ASCT BM aspirate and day 100 post-ASCT BM aspirate 7. Progression-free survival (PFS) and progression-free survival 2 (PFS2) – measured by review of patient data to determine if there has been a recorded death or disease relapse - time point from time of randomisation to date of death or disease progression for duration of follow-up 7. Time to next treatment - measured by review of patient data to determine if the patient has started a new line of therapy – time point from time of randomisation to date of the start of the next treatment for duration of follow-up 8. Overall survival (OS) – measured by review of patient data to determine if there has been a patient | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed