- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04795882
A New Study Evaluating the Activity of Modular CAR T for mYeloma (MCARTY)
An Open Label, Phase 1 Study Evaluating the Activity of Modular CAR T for mYeloma
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 10^6 cells). If the lower dose is deemed tolerable, recruitment into cohort 1 at a higher dose (150 x 10^6 BCMA CAR T cells) and cohort 2 at a dose of 50 x 10^6 BCMA/CD19 cells will begin in parallel.
- 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.
- If both 150 x 10^6 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 10^6 cells.
- If 150 x 10^6 cells BCMA CAR is intolerable and 50 x 10^6 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)
- Dose level 1: 50x10^6 BCMA CAR-T cells
- Dose level 2: 150x10^6 BCMA CAR-T cells
Cohort 2 (BCMA/CD19 CAR-T cells)
- Dose level 1: 50x10^6 BCMA/CD19 CAR-T cells
- Dose level 2: 150x10^6 BCMA/CD19 CAR-T cells
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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County (optional)
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London, County (optional), United Kingdom
- University College London Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18
- Relapsed/Refractory Multiple Myeloma
- Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
- ≥3 prior lines of therapies (including proteasome inhibitor, IMiD, anti CD38 antibody)
- 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)
- Has previously received or is not suitable for ASCT
- Eastern Cooperative Oncology Group (ECOG) performance status 0/1
- Creatinine Clearance (CrCl)≥60ml/min, Absolute Neutrophil Count (ANC)≥1x10^9/L, Platelets (plt)≥50x10^9/L, Haemoglobin (Hb)≥80 /L, lymphocyte count ≥0.3x10^9/L
- Patients must weigh >30 kg
- Agreement to have a pregnancy test, use adequate contraception (if applicable)
- Written informed consent
Exclusion Criteria:
- Previous diagnosis of systemic light chain amyloidosis
- Prior treatment with investigational or approved gene therapy or cell therapy products or allogenic stem cell transplant will be excluded
Stem cell transplant patients only:
- allogeneic stem cell transplant within 12 months prior to registration into the study
- moderate/ severe chronic GVHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
- Oxygen saturation ≤ 90% on air
- Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
- Left ventricular ejection fraction < 50% (ECHO or MUGA)
- Corrected QT interval (QTc)>470 ms on ECG
- Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
- History or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at preconditioning
- Chronic renal impairment requiring dialysis, or creatinine clearance <60ml/min
- 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)
- Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
- Patients with active gastrointestinal bleeding
- Patients with active infectious bacterial or viral disease requiring treatment
- 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
- Patients receiving corticosteroids at a dose of >5 mg prednisolone per day (or equivalent) that cannot be discontinued
- Use of rituximab (or rituximab biosimilar) within the last 3 months prior to CAR T-cell infusion
- Active autoimmune disease requiring immunosuppression
- Past or current history of other neoplasms
- 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
- Patients with any anti-myeloma therapy within the last 7 days prior to LD or leukapheresis
- Inability to tolerate leucapheresis
- Life expectancy <3 months
- Women who are pregnant or breastfeeding
- Known allergy to albumin or DMSO
For CAR T-cell infusion:
- 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
- Requirement for supplementary oxygen at the time of scheduled CAR-T cell infusion
- Clinical deterioration of organ functions (hepatic or renal function) exceeding criteria set at study entry
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: BCMA CAR T cells
Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA CAR T-cells
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Infusion with ATIMP: BCMA CAR T-cells
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Experimental: Cohort 2: BCMA/CD19 CAR T cells
Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA/CD19 CAR T-cells
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Infusion with ATIMP: BCMA/CD19 CAR T-cells
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the Advanced Therapy Investigational Product (ATIMP)
Time Frame: 28 days
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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
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28 days
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Feasibility of manufacturing CAR T-cells evaluated by the number of therapeutic products generated
Time Frame: 30 days
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Feasibility of generation of CAR T cells as evaluated by the number of therapeutic products generated.
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30 days
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
Other Study ID Numbers
- UCL 129642
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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