Clinical trial NCT04309981: Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Institut d'Investigacions Biomèdiques August Pi i Sunyer
Sponsor class: OTHER
Collaborators: name: Fondos ARI (Assistencia Recerca Intensiva)
name: Instituto de Salud Carlos III
name: Fondo Social La Caixa
First posted: 2020-03-17
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 3 months
measure: Cytokine release syndrome rate
timeFrame: within 30 days of first infusion
Secondary outcomes:
measure: Duration of the response
timeFrame: up to 36 months after treatment
measure: Response rate
timeFrame: over the first year
measure: Complete response rate (CR)
timeFrame: at month 3 and month 6 of first infusion
measure: Overall response rate (ORR)
timeFrame: at month 6 of first infusion
measure: Time to complete response
timeFrame: up to 36 months after treatment
measure: Response rate of extramedullary disease by PET-CT
timeFrame: up to 36 months after treatment
measure: Negative MRD rate in bone marrow
timeFrame: at month 3 and month 6 of first infusion
measure: Response rate of extramedullary disease by PET-TC
timeFrame: at month 3
measure: Progression free survival (PFS)
timeFrame: at month 12, and up to 36 months after treatment
measure: Overall survival (OS) defined as the time elapsed between the infusion of ARI0002h and the death of the patient from any cause
timeFrame: up to 36 months after treatment
measure: Presence of tumor lysis syndrome
timeFrame: up to 36 months after treatment
measure: Presence of cytokine release syndrome
timeFrame: up to 36 months after treatment
measure: Presence of neurological toxicity
timeFrame: up to 36 months after treatment
measure: Presence of prolonged cytopenia
timeFrame: up to 36 months after treatment
measure: Persistence of CART BCMA ARI0002 in peripheral blood
timeFrame: month 1, 2, 3, 4, 5, 6 and every 6 months until 2 years of follow up
measure: Expression of BCMA
timeFrame: at screening, at day +28, at day +100, at month 6, 12, 18 and 24
measure: Levels of soluble BCMA in serum
timeFrame: 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
Other outcomes:
Locations:
city: Santiago De Compostela
country: Spain
facility: Hospital U. de Santiago de Compostela
state: A Coruña
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de La Arrixaca
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Carlos Fernandez de Larrea, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.