A Single Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.
- Conditions
- Multiple myeloma or cancer of white blood cells10035227
- Registration Number
- NL-OMON47144
- Lead Sponsor
- Autolus Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 27
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.
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 *mol/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. G-CSF 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For Phase I:<br /><br>1. Incidence of Grade 3 to 5 toxicity occurring within the dose-limiting<br /><br>toxicity (DLT) period (28 days post AUTO2 infusion).<br /><br>2. Frequency of dose limiting toxicity (DLT) and the persistence of AUTO2.<br /><br><br /><br>For Phase II:<br /><br>1. Best overall response post-AUTO2 infusion.<br /><br>2. Frequency and severity of AEs and SAEs.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Proportion of patients for whom an AUTO2 product can be generated<br /><br>(feasibility).<br /><br>2. Determine the clinical benefit (stringent complete response + complete<br /><br>response + very good partial response + partial response + minor response<br /><br>[sCR+CR+VGPR+PR+MR]) rate following treatment with AUTO2.<br /><br>3. To evaluate clinical outcomes including duration of response, time to<br /><br>disease progression, PFS and OS.<br /><br>4. Quantitative PCR (qPCR) and/or flow cytometry at a range of time points in<br /><br>the peripheral blood.</p><br>