A randomised trial of Daratumumab to remove myeloma cells from blood stem cells before an autograft for patients with multiple myeloma

Phase 1

• Conditions: ewly diagnosed Multiple Myeloma (MM); MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002147-20-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-08-27
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 338

Inclusion Criteria

•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
•Received only 1st line induction therapy (i.e., undergoing or completed first line therapy at the time of enrolment).*
•Induction with either VCD or VTD**
•Received Bortezomib-containing induction treatment for at least 4 cycles
•Achieving at least PR following induction treatment
•Considered suitable for ASCT at the time of entering the trial as clinically judged by the local Investigator
•ECOG =2, (Appendix 3) unless related to myeloma
•Age =18
•Creatinine clearance =30ml/min
•Adults of reproductive potential must agree to use effective contraception or maintain abstinence for 6 months after therapy
•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 proposed by [1], 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.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 298
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

•Previous treatment with Daratumumab or other anti-CD38 therapies
•Demonstrating evidence of progressive disease according to IMWG criteria
•Peripheral neuropathy above grade 2 as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
•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 •Bilirubin >2 x upper limit of normal (ULN)
•ALT/AST >3 x ULN
•Known chronic obstructive pulmonary disease (COPD), persistent asthma or pulmonary function tests showing Forced Expiratory Volume (FEV1) <60%
•Known cardiac impairment with Left Ventricular Ejection Fraction (LVEF) <50%
•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)
•POEMS syndrome, plasma cell leukaemia, amyloidosis (AL), smouldering multiple myeloma, Waldenstroms macroglobulinaemia.
•Known or suspected central nervous system (CNS) involvement by myeloma
•Radiation therapy within 4 weeks of trial entry
•Participation in an investigational therapeutic study within the 4 weeks prior to first dose of Daratumumab
•Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to trial entry
•Known or suspected human immunodeficiency virus (HIV) infection or subjects who are HIV seropositive
•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)
•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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified