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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Biological: Adult differentiated autologous T-cells with anti-BCMA specificity

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic of Barcelona
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Murcia, Spain, 30120
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • A Coruña
    • Santiago De Compostela, A Coruña, Spain, 15706
      • Hospital U. de Santiago de Compostela
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARI0002h; 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; After pretreatment, adult differentiated autologous T-cells with a chimeric antigen receptor with anti-BCMA specificity will be transfused.; Other Names: CARTBCMA

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sara V. Latorre
• Collaborators: Instituto de Salud Carlos III; Fondos ARI (Assistencia Recerca Intensiva); Fondo Social La Caixa
• Investigators: Principal Investigator: Carlos Fernandez de Larrea, MD,PhD, Hospital Clinic of Barcelona

Publications and helpful links

General Publications

• Oliver-Caldes A, Jimenez R, Espanol-Rego M, Cibeira MT, Ortiz-Maldonado V, Quintana LF, Castillo P, Guijarro F, Tovar N, Montoro M, Benitez-Ribas D, Bataller A, Gonzalez-Navarro EA, Cid J, Lozano M, Perez-Amill L, Martin-Antonio B, Mena MP, Moreno DF, Rodriguez-Lobato LG, Campistol JM, Calvo G, Blade J, Rosinol L, Juan M, Pascal M, Urbano-Ispizua A, Fernandez de Larrea C. First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma. J Immunother Cancer. 2021 Dec;9(12):e003783. doi: 10.1136/jitc-2021-003783. Erratum In: J Immunother Cancer. 2022 Nov;10(11):

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: July 1, 2023

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: CARTBCMA-HCB-01; 2019-001472-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No