Modular BCMA and BCMA/CD19 CAR T therapy for relapsed or refractory multiple myeloma

An Open Label, Phase 1 Study Evaluating the Activity of Modular CAR T for mYeloma

This Phase 1 trial will test two CAR T approaches—BCMA-only and BCMA-plus-CD19—in adults with relapsed or refractory multiple myeloma who have had at least three prior treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University College, London (Academic / other)
• Drugs / interventions: CAR-T, radiation, CAR T, Chimeric Antigen Receptor
• Locations: 1 site (London, County (Optional))
• Trial ID: NCT04795882 on ClinicalTrials.gov

What this trial studies

This Phase 1 rolling-6 dose-escalation study enrolls adults with relapsed/refractory secretory multiple myeloma to receive either BCMA-directed CAR T cells or CAR T cells co-expressing BCMA and CD19. Patients enter cohort 1 (BCMA alone) or cohort 2 (BCMA/CD19) with stepwise dose levels (50 x 10^6, 150 x 10^6, and a potential 450 x 10^6 cell level) and predefined rules to expand or stop cohorts based on tolerability. The trial tests feasibility of manufacturing the cellular products and monitors safety closely around infusion, with inpatient observation and scheduled follow-up for adverse events and response. Dose escalation can proceed in parallel for the two products, with escalation contingent on observed toxicity in each cohort.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory secretory multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody, and who meet organ-function and ECOG 0–1 requirements are the intended participants.

Not a fit: Patients with prior systemic light-chain amyloidosis, inadequate blood counts or organ/renal function, uncontrolled infection, or who cannot undergo leukapheresis or required inpatient procedures are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could provide deeper or longer remissions for patients whose myeloma no longer responds to standard therapies.

How similar studies have performed: BCMA-directed CAR T therapies have produced significant responses in relapsed myeloma in prior trials, while dual BCMA/CD19 CAR approaches remain more experimental with limited clinical data.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18
2. Relapsed/Refractory Multiple Myeloma
3. Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
4. ≥3 prior lines of therapies (including proteasome inhibitor, IMiD, anti CD38 antibody)
5. 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)
6. Has previously received or is not suitable for ASCT
7. Eastern Cooperative Oncology Group (ECOG) performance status 0/1
8. 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
9. Patients must weigh \>30 kg
10. Agreement to have a pregnancy test, use adequate contraception (if applicable)
11. Written informed consent

Exclusion Criteria:

1. Previous diagnosis of systemic light chain amyloidosis
2. Prior treatment with investigational or approved gene therapy or cell therapy products
3. 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
4. Oxygen saturation ≤ 90% on air
5. Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
6. Left ventricular ejection fraction \< 50% (ECHO or MUGA)
7. Corrected QT interval (QTc)\>470 ms on ECG
8. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
9. History or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at preconditioning
10. Chronic renal impairment requiring dialysis
11. 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)
12. Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
13. Patients with active gastrointestinal bleeding
14. Patients with active infectious bacterial or viral disease requiring treatment
15. 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
16. Patients receiving corticosteroids at a dose of \>5 mg prednisolone per day (or equivalent) that cannot be discontinued
17. Active autoimmune disease requiring immunosuppression
18. Past or current history of other neoplasms
19. 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
20. Patients with any anti-myeloma therapy within the last 7 days prior to LD or leukapheresis
21. Inability to tolerate leucapheresis
22. Life expectancy \<3 months
23. Women who are pregnant or breastfeeding
24. Known allergy to albumin or DMSO

Exclusion criteria for CAR-T cell infusion:

1. 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
2. Requirement for supplementary oxygen at the time of scheduled CAR-T cell infusion
3. Clinical deterioration of organ functions (hepatic or renal function) exceeding criteria set at study entry

Where this trial is running

London, County (Optional)

• University College London Hospital — London, County (Optional), United Kingdom (Recruiting)

Study contacts

• Study coordinator: MCARTY Trial Coordinator

Conditions Multiple Myeloma