Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.

Study Overview
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Brief Summary
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To assess the safety and efficacy of CARTBCMA ARI0002h in patients with relapsed/refractory multiple myeloma who have received treatment with proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

Official Title
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Pilot Study of the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-BCMA (TNFRSF17) Specificity Humanized Conjugated With the Co-stimulatory Region 4-1BB and Signal-transduction CD3z (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma With Previous Treatment With Proteasome Inhibitor, Immunomodulatory Drug and Anti-CD38 Monoclonal Antibody

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: Adult differentiated autologous T-cells with anti-BCMA specificity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between the age of 18 and 75 years with diagnosis of multiple myeloma Disease measurable by monoclonal component in serum and/or urine or by free light chains in serum according to the eligibility criteria for clinical trials of the International Myeloma Working Group Previous two or more lines of treatment. Patients must have received at least a proteasome inhibitor (such as bortezomib or carfilzomib), an immunomodulatory drug (lenalidomide or pomalidomide) and an anti-CD38 monoclonal antibody (such as daratumumab) Refractory to the last line of treatment ECOG functional status ranging from 0 to 2 Life expectancy over 3 months Patients who, after being informed, give their consent by signing the Informed Consent document. Exclusion Criteria: Previous allogeneic transplant in the prior 6 months to inclusion or GVHD that requires active systemic immunosuppressive treatment Absolute lymphocyte count <0.1x10^9/ L Previous neoplasia, except if patients have been in complete remission > 3 years, except for cutaneous carcinoma (non-melanoma) Active infection that requires treatment Active infection by HIV, HBV or HCV. Uncontrolled medical disease Severe organic condition that meets any of the following criteria: EF <40%, DLCO <40%, EGFR <50 ml / min, bilirubin> 3 times normal value (except Gilbert syndrome) Previous diagnosis of symptomatic AL amyloidosis Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test in the screening phase Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who cannot or do not wish to use highly effective contraceptive methods from the beginning until the end of the study. Men who cannot or do not wish to use highly effective contraceptive methods from the beginning to the end of the study. Contraindication to receive conditioning chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARI0002h<br>Adult differentiated autologous T-cells from peripheral blood, expanded and transducted with a lentivirus to express a chimeric antigen receptor with anti-BCMA (TNFRSF17) specificity conjugated to the 4-1BB co-stimulatory region and signal-transduction CD3z that has been humanized | Biological: Adult differentiated autologous T-cells with anti-BCMA specificity<br>* After pretreatment, adult differentiated autologous T-cells with a chimeric antigen receptor with anti-BCMA specificity will be transfused.<br>* Other names: CARTBCMA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | 3 months | 
| Cytokine release syndrome rate |  | within 30 days of first infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of the response |  | up to 36 months after treatment | 
| Response rate |  | over the first year | 
| Complete response rate (CR) |  | at month 3 and month 6 of first infusion | 
| Overall response rate (ORR) |  | at month 6 of first infusion | 
| Time to complete response |  | up to 36 months after treatment | 
| Response rate of extramedullary disease by PET-CT |  | up to 36 months after treatment | 
| Negative MRD rate in bone marrow |  | at month 3 and month 6 of first infusion | 
| Response rate of extramedullary disease by PET-TC |  | at month 3 | 
| Progression free survival (PFS) |  | at month 12, and up to 36 months after treatment | 
| Overall survival (OS) defined as the time elapsed between the infusion of ARI0002h and the death of the patient from any cause |  | up to 36 months after treatment | 
| Presence of tumor lysis syndrome |  | up to 36 months after treatment | 
| Presence of cytokine release syndrome |  | up to 36 months after treatment | 
| Presence of neurological toxicity |  | up to 36 months after treatment | 
| Presence of prolonged cytopenia |  | up to 36 months after treatment | 
| Persistence of CART BCMA ARI0002 in peripheral blood |  | month 1, 2, 3, 4, 5, 6 and every 6 months until 2 years of follow up | 
| Expression of BCMA |  | at screening, at day +28, at day +100, at month 6, 12, 18 and 24 | 
| Levels of soluble BCMA in serum |  | at screening, at day 0, +3, +7,+14,+28, +70 +100, at month 4, 5, 6, 7, 8, 9, 1,11, 12, 18 and 24 |