A New Study Evaluating the Activity of Modular CAR T for mYeloma (MCARTY)

University College London (UCL)

Status and phase

Active, not recruiting

Phase 1

Conditions

Multiple Myeloma

Treatments

Biological: BCMA CAR T cells

Biological: BCMA/CD19 CAR T cells

Study type

Interventional

Funder types

Other

Identifiers

NCT04795882

UCL 129642

Details and patient eligibility

About

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.

Full 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

Enrollment

24 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)≥40ml/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