Multiple myeloma or cancer of white blood cells
Conditions
Interventions
Eligible patients will receive a single dose IV of AUTO2 following
pre-conditioning treatment.
Five dose cohorts are planned in Phase I:
- Cohort 1, Dose Level 1: 15 x 10e6 RQR8/APRIL CAR positive T
Chimeric Antigen Receptor (CAR)-T cell
dose-response relationship
Multiple myeloma
safety
Sponsors
Autolus Limited
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients, aged * 18. 2. Willing and able to give written, informed consent for the current study protocol, AUTO2-MM1. 3. Confirmed diagnosis of MM as per IMWG. 4. Measurable disease as defined by any one of the following: - Serum M-protein * 500 mg/dL; - Urine M-protein * 200 mg/24 hours; - Involved serum free light chain level * 10 mg/dL, provided serum free light chain ratio is abnormal. 5. Relapsed or refractory disease after either one of the following: a. Had at least 3 different prior lines of therapy including proteasome inhibitor (e.g. bortezomib or carfilzomib), immunomodulatory therapy (IMiD; e.g. thalidomide, lenalidomide or pomalidomide) and alkylator or monoclonal antibody OR b. Have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of receiving these agents. 6. For females of childbearing potential (defined as less than 2 years after last menstruation or not surgically sterile), a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1. 8. Peripheral blood total lymphocyte count > 0.5 x 10e9/L at enrolment and prior to leukapheresis.
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or lactating. 2. Prior treatment with investigational or approved gene therapy or cell therapy products. 3. Clinically significant, uncontrolled heart disease (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick-sinus syndrome, or electrocardiographic evidence of acute ischaemia or Grade 3 conduction system abnormalities unless the patient has a pacemaker) or a recent (within 6 months) cardiac event. 4. Left Ventricular Ejection fraction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For Phase I: 1. Incidence of Grade 3 to 5 toxicity occurring within the dose-limiting toxicity (DLT) period (28 days post AUTO2 infusion). 2. Frequency of dose limiting toxicity (DLT) and the persistence of AUTO2. For Phase II: 1. Best overall response post-AUTO2 infusion. 2. Frequency and severity of AEs and SAEs. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients for whom an AUTO2 product can be generated (feasibility). 2. Determine the clinical benefit (stringent complete response + complete response + very good partial response + partial response + minor response [sCR+CR+VGPR+PR+MR]) rate following treatment with AUTO2. 3. To evaluate clinical outcomes including duration of response, time to disease progression, PFS and OS. 4. Quantitative PCR (qPCR) and/or flow cytometry at a range of time points in the peripheral blood. | — |
Countries
United Kingdom, United States of America
Outcome results
None listed