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

Relapsed/Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04309981
• Other study ID #: CARTBCMA-HCB-01
• Secondary ID: 2019-001472-11
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 27, 2020
• Est. completion date: April 1, 2025

Study information

• Verified date: July 2023
• Source: Institut d'Investigacions Biomèdiques August Pi i Sunyer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 73
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Clinic of Barcelona	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clínico Universitario Virgen de La Arrixaca	Murcia
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital U. de Santiago de Compostela	Santiago De Compostela	A Coruña
Spain	Hospital Universitario Virgen Del Rocío	Sevilla

Sponsors (4)

Lead Sponsor	Collaborator
Sara V. Latorre	Fondo Social La Caixa, Fondos ARI (Assistencia Recerca Intensiva), Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)		3 months
Primary	Cytokine release syndrome rate		within 30 days of first infusion
Secondary	Duration of the response		up to 36 months after treatment
Secondary	Response rate		over the first year
Secondary	Complete response rate (CR)		at month 3 and month 6 of first infusion
Secondary	Overall response rate (ORR)		at month 6 of first infusion
Secondary	Time to complete response		up to 36 months after treatment
Secondary	Response rate of extramedullary disease by PET-CT		up to 36 months after treatment
Secondary	Negative MRD rate in bone marrow		at month 3 and month 6 of first infusion
Secondary	Response rate of extramedullary disease by PET-TC		at month 3
Secondary	Progression free survival (PFS)		at month 12, and up to 36 months after treatment
Secondary	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
Secondary	Presence of tumor lysis syndrome		up to 36 months after treatment
Secondary	Presence of cytokine release syndrome		up to 36 months after treatment
Secondary	Presence of neurological toxicity		up to 36 months after treatment
Secondary	Presence of prolonged cytopenia		up to 36 months after treatment
Secondary	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
Secondary	Expression of BCMA		at screening, at day +28, at day +100, at month 6, 12, 18 and 24
Secondary	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