Relapsed/Refractory Multiple Myeloma
Conditions
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.
Interventions
BIOLOGICALAdult 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.
Sponsors
Fondos ARI (Assistencia Recerca Intensiva)
Instituto de Salud Carlos III
Fondo Social La Caixa
Sara V. Latorre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate (ORR) | 3 months |
| Cytokine release syndrome rate | within 30 days of first infusion |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Duration of the response | 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 |
| 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 |
| Response rate | over the first year |
Countries
Spain
Outcome results
None listed