Relapsed or Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864 MedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: AUTO2
Product Code: AUTO2
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: n/a
CAS Number: n/a
Sponsors
Autolus Limited
Eligibility
Sex/Gender
All
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. 4. Measurable disease as defined by any 1 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. Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g. bortezomib or carfilzomib) and 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 0.5 x 10e9/L at enrolment and prior to leukapheresis Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 47
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 < 50 (by ECHO or MUGA) unless the institutional lower limit of normal is lower. 5. Patients with a history or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning. 6. Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted. 7. Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3 × ULN, or total bilirubin =25 µmol/L (1.5 mg/dL), except in patients with Gilbert’s syndrome or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy). 8. Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min. 9. Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatment. 10. Use of rituximab (or rituximab biosimilars) within the last 3 months prior to AUTO2 infusion. 11. Active autoimmune disease requiring immunosuppression. 12. Received any anti-myeloma therapy within the last 7 days prior to pre-conditioning or leukapheresis. Growth factors should stop 10 days prior to leukapheresis. 13. Received any radiotherapy within the last 7 days prior to pre-conditioning or leukapheresis. Localised radiation to a single site, e.g. for bone pain is permitted at any time. 14. Life expectancy < 3 months. 15. Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: Assess the safety and tolerability of AUTO2, establish the recommended Phase II dose & maximum tolerated dose, where applicable. Phase 2: To evaluate the anti-tumour effect, safety and tolerability of AUTO2. ; Secondary Objective: - Evaluate the feasibility of generating the ATIMP - Evaluate the clinical efficacy of AUTO2 - Assess biomarker and pharmacodynamics effects of AUTO2 ; Primary end point(s): Phase 1: Incidence of Grade 3-5 toxicity occurring within the dose-limiting toxicity (DLT) period (28 days post AUTO2 infusion). Frequency of DLT and the persistence of AUTO2. Phase 2: Best overall response post-AUTO2 infusion. Frequency and severity of AEs and SAEs. ; Timepoint(s) of evaluation of this end point: Phase 1: 28 days post AUTO2 infusion and 24 months post-AUTO2 administration of the last patient. Phase 2: From patient dosing up to 26 months post-AUTO2 administration of the last patient unless in the event of death or early withdraw, which would default to the preceding patient's completion timepoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients for whom an AUTO2 product can be generated (feasibility). •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. •To evaluate clinical outcomes including duration of response, time to disease progression, PFS and OS. Quantitative PCR (qPCR) and/or flow cytometry at a range of time points in the peripheral blood . ;Timepoint(s) of evaluation of this end point: From patient dosing up to 24 months following AUTO2 infusion, or in the event of an earlier outcome on the last patient entered onto the study. | — |
Countries
Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Project Manager
Autolus Limited
Outcome results
None listed