Clinical Trial Using Humanized CART Directed Against BCMA (ARI0002h) in Patients With Relapsed/Refractory Multiple Myeloma to Proteasome Inhibitors, Immunomodulators and Anti-CD38 Antibody.
Phase 1
Active, not recruiting
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Biological: Adult differentiated autologous T-cells with anti-BCMA specificity
- Registration Number
- NCT04309981
- Lead Sponsor
- Sara V. Latorre
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 73
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ARI0002h Adult differentiated autologous T-cells with anti-BCMA specificity 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
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) 3 months Cytokine release syndrome rate within 30 days of first infusion
- Secondary Outcome Measures
Name Time Method 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 Response rate over the first year Response rate of extramedullary disease by PET-TC at month 3 Presence of tumor lysis syndrome up to 36 months after treatment Presence of neurological toxicity 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 Duration of the response up to 36 months after treatment Time to complete response up to 36 months after treatment Expression of BCMA at screening, at day +28, at day +100, at month 6, 12, 18 and 24 Complete response rate (CR) at month 3 and month 6 of first infusion Overall response rate (ORR) at month 6 of first infusion 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 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 cytokine release syndrome up to 36 months after treatment Presence of prolonged cytopenia up to 36 months after treatment
Trial Locations
- Locations (7)
Hospital Universitario Virgen Del Rocío
🇪🇸Sevilla, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Clínico Universitario Virgen de La Arrixaca
🇪🇸Murcia, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinic of Barcelona
🇪🇸Barcelona, Spain
Hospital U. de Santiago de Compostela
🇪🇸Santiago De Compostela, A Coruña, Spain