The study proposed here intends to evaluate the safety and efficacy of escalating doses of autologous PMCC-COE-KMA CAR T-cells administered to patients with relapsed/refractory multiple myeloma that expresses the KMA. The PMCC-COE-KMA CAR T-cells will be produced using LV and administered to patients after lymphodepleting conditioning chemotherapy. Considering the poor prognosis of myeloma patients who have relapsed after ≥ 2 lines of therapy, combined with evidence of PMCC-COE-KMA CAR T-cell specificity, as well as the efficacy and manageable toxicity of PMCC-COE-KMA, investigators believe the potential benefits outweigh the risks of this trial.
Patient has provided written informed consent using the KOALA Patient Information and Consent Form (PICF)
Age ≥ 18 years on the day of signing informed consent form
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2 (Appendix 2)
Life expectancy of ≥ 3 months, as assessed by the Investigator
A diagnosis of lambda-restricted MM
Plasma cell leukaemia at the time of Screening (> 5% circulating plasma cells by standard differential), Waldenström's macroglobulinaemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis
Known active, or prior history of, central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM
Major surgery within 4 weeks prior to registration
Sequential
PMCC-COE-KMA
Biological/VaccinePMCC-COE-KMA is a cellular immunotherapy derived from autologous mononuclear cells that have undergone ex vivo modification to target KMA on the surface of cancer cells. Autologous T-cells are genetically programmed using LV transduction to express a CAR, which comprises an antigen recognition moiety liked to a T-cell receptor signalling domain. This makes the CAR T-cells capable of recognising KMA on tumour cells and triggering target cell destruction in a major histocompatibility complex-independent manner.
To evaluate the safety of autologous PMCC-COE-KMA in patients with RR MM following lymphodepletion, identifying the maximum tolerated dose (MTD)
* Incidence, nature, and severity of "moderate" toxicity (MT) events and dose limiting toxicities (DLTs) These will determine the MTD of PMCC-COE-KMA * Incidence, nature, and severity of AEs graded according to the Common Toxicity Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) and the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for CRS and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), and serious adverse events (SAEs)
To assess manufacturing feasibility of PMCC-COE-KMA, defined as the percentage of patients in whom a suitable product manufactured, meeting pre-determined criteria for release.
The patient has a suitable product manufactured, meeting pre-determined criteria for release (yes/no). The percentage of patients with this feasible manufacture will be reported.
To evaluate the efficacy of PMCC-COE-KMA, as assessed by ORR based on the International Myeloma Working Group (IMWG) response criteria
* Objective response after the PMCC-COE-KMA infusion, measured every 28 days following the infusion of PMCC-COE-KMA by IMWG criteria * Best overall response * Duration of response, defined as time from first response of stringent complete response (sCR), CR, very good partial response (VGPR) or PR to time to progressive disease (PD) by IMWG criteria (death is a censoring event), for those patients who experience a sCR, CR, VGPR or PR
To evaluate the efficacy of PMCC-COE-KMA, as assessed by minimal residual disease (MRD) at defined time points
Minimal residual disease response by flow cytometry and/or molecular techniques on bone marrow aspirate at Day +28 and at suspected CR
To evaluate the efficacy of PMCC-COE-KMA, as progression-free survival
Progression-free survival, defined as time from registration until biochemical, radiological and/or clinical PD or death, according to IMWG criteria. Patients without PD or death will be censored at their last time of disease assessment
To evaluate the efficacy of PMCC-COE-KMA as overall survival (OS) analyses
Overall survival, defined as time from study enrolment to death. Patients without death will be censored at the earliest of the study close out date or date last seen alive
To evaluate the T-cell phenotype of the PMCC-COE-KMA infusion product
Immunophenotype of the PMCC-COE-KMA infusion product by flow cytometry and/or single-cell multi-omic assays
To evaluate the expansion and persistence of autologous PMCC-COE-KMA in blood and bone marrow after infusion
PMCC-COE-KMA expansion and persistence kinetics in peripheral blood, as measured by flow cytometry and/or a quantitative polymerase chain reaction (PCR)
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Peter MacCallum Cancer Centre, Australia
Lead sponsor
HaemalogiX Ltd
Collaborator
