Phase I/II study evaluating AUTO2 in patients with multiple myeloma

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003893-42-GB
• Lead Sponsor: Autolus Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-10-25
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 80

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 < 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
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

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.

Study & Design

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