MCARTY: A New Study Evaluating the Activity of Modular CAR T for mYeloma
Study Details
Study Description
Brief Summary
This is a Phase 1 rolling 6 trial design evaluating safety of a novel BCMA Chimeric Antigen Receptor (CAR) alone and of CAR T cells engineered to co-express BCMA CAR and a CD19 CAR in patients with relapsed / refractory Multiple Myeloma.
The study will assess the feasibility of generating these Advanced Therapy Investigational Products (ATIMPs) and the safety of administering the CAR T cells (either BCMA alone or co-expressed with CD19) in patients with relapsed / refractory multiple myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a Phase 1 rolling 6 trial design evaluating safety of a novel BCMA CAR alone and of CAR T cells engineered to co-express BCMA CAR and a CD19 CAR in patients with triple refractory Multiple Myeloma.
The first 3-6 patients will be treated at the lower dose of BCMA CAR T cells in cohort 1 (50 x 106 cells). If the lower dose is deemed tolerable, recruitment into cohort 1 at a higher dose (150 x 106 BCMA CAR T cells) and cohort 2 at a dose of 50 x 10^6 BCMA/CD19 cells will begin in parallel.
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If the 50 x 10^6 cells BCMA/CD19 CAR dose in cohort 2 is deemed intolerable, then no further patients will be recruited to cohort 2.
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If both 150 x 106 cells BCMA CAR (cohort 1) and 50 x 106 cells BCMA/CD19 CAR (cohort 2) are deemed tolerable then recruitment will begin to a higher BCMA/CD19 CAR dose of 150 x 106 cells.
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If 150 x 106 cells BCMA CAR is intolerable and 50 x 106 cells BCMA/CD19 CAR is tolerable then no further patients will be recruited to cohorts 1 or 2.
A Summary of dosing on trial is outlined below:
Cohort 1 (BCMA CAR-T cells)
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Dose level 1: 50x10^6 BCMA CAR-T cells
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Dose level 2: 150x10^6 BCMA CAR-T cells
Cohort 2 (BCMA/CD19 CAR-T cells)
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Dose level 1: 50x10^6 BCMA/CD19 CAR-T cells
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Dose level 2: 150x10^6 BCMA/CD19 CAR-T cells
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: BCMA CAR T cells Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA CAR T-cells |
Biological: BCMA CAR T cells
Infusion with ATIMP: BCMA CAR T-cells
|
| Experimental: Cohort 2: BCMA/CD19 CAR T cells Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA/CD19 CAR T-cells |
Biological: BCMA/CD19 CAR T cells
Infusion with ATIMP: BCMA/CD19 CAR T-cells
|
Outcome Measures
Primary Outcome Measures
- Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the Advanced Therapy Investigational Product (ATIMP) [28 days]
The incidence of grade 3-5 toxicity assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and the American Society for Transplantation and Cellular Therapy (ASTCT) Cytokine Release Syndrome (CRS) and Neurotoxicity tool
- Feasibility of manufacturing CAR T-cells evaluated by the number of therapeutic products generated [30 days]
Feasibility of generation of CAR T cells as evaluated by the number of therapeutic products generated.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18
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Relapsed/Refractory Multiple Myeloma
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Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
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≥3 prior lines of therapies (including proteasome inhibitor, IMiD, anti CD38 antibody)
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Refractory to last line of therapy (not achieved at least PR and progressed within 60 days of last dose or achieved at least PR but progressed within 6 months of last dose)
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Has previously received or is not suitable for ASCT
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Eastern Cooperative Oncology Group (ECOG) performance status 0/1
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Creatinine Clearance (CrCl)≥60ml/min, Absolute Neutrophil Count (ANC)≥1x109/L, Platelets (plt)≥50x109/L, Haemoglobin (Hb)≥80 /L, lymphocyte count ≥0.3x10^9/L
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Patients must weigh >30 kg
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Agreement to have a pregnancy test, use adequate contraception (if applicable)
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Written informed consent
Exclusion Criteria:
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Previous diagnosis of systemic light chain amyloidosis
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Prior treatment with investigational or approved gene therapy or cell therapy products or allogenic stem cell transplant will be excluded
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Stem cell transplant patients only:
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allogeneic stem cell transplant within 12 months prior to registration into the study
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moderate/ severe chronic GVHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
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Oxygen saturation ≤ 90% on air
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Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
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Left ventricular ejection fraction < 50% (ECHO or MUGA)
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Corrected QT interval (QTc)>470 ms on ECG
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Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
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History or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at preconditioning
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Chronic renal impairment requiring dialysis, or creatinine clearance <60ml/min
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Patients with significant liver disease: alanine aminotransferase or aspartate aminotransferase ≥3x upper limit normal (ULN), or total bilirubin ≥25umol/L (1.5mg/dL), except in patients with Gilbert's syndrome, or evidence of end-stage liver disease (e.g. ascites, hepatic encephalopathy)
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Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
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Patients with active gastrointestinal bleeding
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Patients with active infectious bacterial or viral disease requiring treatment
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Known active central nervous system involvement of MM. 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
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Patients receiving corticosteroids at a dose of >5 mg prednisolone per day (or equivalent) that cannot be discontinued
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Use of rituximab (or rituximab biosimilar) within the last 3 months prior to CAR T-cell infusion
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Active autoimmune disease requiring immunosuppression
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Past or current history of other neoplasms
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Received any radiotherapy within the last 7 days prior to lymphodepletion or leukapheresis. Localised radiation to a single site, e.g. for bone pain is permitted at any time
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Patients with any anti-myeloma therapy within the last 7 days prior to LD or leukapheresis
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Inability to tolerate leucapheresis
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Life expectancy <3 months
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Women who are pregnant or breastfeeding
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Known allergy to albumin or DMSO
For CAR T-cell infusion:
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Active infection requiring systemic anti-microbial therapy, or with temperature more or equal to 38 C within 48 hours before scheduled CAR-T cell infusion
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Requirement for supplementary oxygen at the time of scheduled CAR-T cell infusion
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Clinical deterioration of organ functions (hepatic or renal function) exceeding criteria set at study entry
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University College, London
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UCL 129642