AL Amyloid Cancer
Conditions
Interventions
There are 2 cohorts in this trial:
Cohort 1 – D8 CAR T cells (CAR T cells targeting BCMA).
Cohort 2 – D8/ CAT CAR T cells (CAR T cells targeting both BCMA and CD19)
Both cohorts have 2 dose levels: 5
Sponsors
University College London Cancer Trials Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years old 2. Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following: 2.1. Immunohistochemistry or 2.2. Mass spectrometry or 2.3. Characteristic electron microscopy appearance or 2.4. Hereditary amyloidosis ruled out by appropriate genetic screening 3. ECOG performance status 0-2 4. Measurable disease defined by at least one of the following: 4.1. Serum free light chain =50 mg/L and an abnormal K:L ratio 4.2. The difference between involved and uninvolved free light chains (dFLC) =50mg/L 4.3. The difference between involved and uninvolved serum free light chain is 20-50mg/L (termed low-dFLC), only if the patients had at diagnosis either iFLC of >50mg/L with abnormal ratio of dFLC>50mg/L 4.4. Serum monoclonal protein =5g/L 5. Patient must have adequate organ function, defined as follows: 5.1. Neutrophils >1x10^9/L 5.2. Haemoglobin >80mg/L 5.3. Platelets >50 x10^9/L 5.4. Lymphocytes >0.3 x10^9/L 5.5. eGFR >30ml/min 5.6. NT-proBNP 100mmHg 6. At least 1 previous line of therapy and relapsed or 30 kg 8. Women of childbearing potential must have a negative pregnancy test and agree to comply with the pregnancy reporting requirements of the protocol (if applicable) 9. Provide written informed consent and be willing and able to comply with all study procedures
Exclusion criteria
Exclusion criteria: 1. Have any other form of amyloidosis other than AL amyloidosis 2. Have POEMS syndrome 3. Have systolic blood pressure 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion 4. Receiving haemodialysis 5. Have had myocardial infarction, uncontrolled angina within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening 6. LVEF is 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed) 9. Corrected QT interval (QTc) > 500 ms on the screening electrocardiogram (ECG) in absence of bundle branch block or paced rhythm 10. Current unstable liver or biliary disease defined by the presence of ascites requiring paracentesis, encephalopathy, coagulopathy, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement due to AL amyloidosis is acceptable if otherwise meets entry criteria 11. Prior treatment with investigational or approved gene therapy or cell therapy products 12. Oxygen saturation = 90% on air 13. Patients with any major surgical intervention in the last 3 months (cement augmentation for vertebral collapse is permitted) 14. Patients with active gastrointestinal bleeding 15. Patients with active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatment 16. Known active central nervous system involvement of AL amyloid or multiple myeloma. History or presence of clinically relevant central nervous system pathology such as epilepsy*, paresis, aphasia, stroke within 3 months prior to enrolment, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis (*patients with well-controlled epilepsy with no seizures within the last 12 months, confirmed by treating neurologist will not be excluded) 17. Active autoimmune disease requiring immunosuppression 18. Patients receiving corticosteroids at a dose of > 5 mg prednisolone per day (or equivalent) that cannot be discontinued 19. Past or current history of other neoplasms (including lymphoma), except for: 19.1. Curatively treated non-melanoma skin cancer 19.2. Adequately treated in situ carcinoma of the cervix 19.3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL 19.4. Other cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: toxicity of D8 or D8/CAT CAR T cells as assessed by the incidence of grade 3-5 toxicity causally related to the ATIMP (particularly severe cytokine release syndrome, neurotoxicity) occurring within 28 days of CAR T cell infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Up to 2 years (unless noted otherwise): 1. Best objective response rate (as defined by ISA criteria) 2. Overall rate of CR, CR rate at 1 month and 3 months 3. Time to first and best sFLC response 4. Time to sFLC-CR 5. Overall rate of MRD-negative(10-5) response 6. Rate of CR with MRD-negativity at 12 ± 3 months 7. Duration of response in patients achieving =PR 8. PFS 9. OS 10. Time to new treatment or death 11. EFS (new treatment, progression or death as events) 12. Organ response at 6 and 12 months 13. Incidence and severity of adverse events 14. Occurrence of neurotoxicity, early and late, considered related to CAR T cells 15. Incidence & duration of hypogammaglobulinaemia (all cohorts) and B-cell aplasia (cohort 2) | — |
Countries
England, United Kingdom
Contacts
Public Contact. ALARIC Trial Manager
Outcome results
None listed