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

Phase 1

• Conditions: Relapsed or Refractory Multiple Myeloma; MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-19
• Study Completion: 2019-09-05
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Male or female patients, aged = 18.
2. Willing and able to give written, informed consent for both, the current study protocol AUTO2-MM1 and the associated long term follow up study AUTO2-LT1.
3. Confirmed diagnosis of MM as per IMWG.
4. Measurable disease as defined by IMWG, 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. At least 2 previous anti myeloma treatments (which between them must have included alkylator therapy, an immunomodulatory drug and a proteasome inhibitor).
6. Relapsed or refractory disease (refractory defined as either progression on previous regimen or progression within 60 days of stopping previous regimen). Relapse as defined by IMWG criteria.
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
9. Peripheral blood total lymphocyte count > 0.5 x 109/L.
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

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 > 2.0 mg/dL 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 21 days prior to pre-conditioning, or 10 days (or = 3 half-lives) prior to leukapheresis steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post dose prior to pre-conditioning or leukapheresis.
13. Received any radiotherapy within the last 21 days prior to pre-conditioning or 10 days prior to leukapheresis. Localised radiation therapy to a single site, e.g. for bone pain within last 7 days is acceptable.
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