The goal of this clinical trial is to learn if anitocabtagene autoleucel following induction therapy works to treat adult participants with newly diagnosed multiple myeloma. The main objectives of this clinical trial are: * To determine the incidence and severity of all adverse events (AEs). * To determine the proportion of patients achieving undetectable minimal residual disease (uMRD) negative-CR rate (minimum 10 to -5) at 12 months (+/- 3 months) after enrollment. Participants will receive induction therapy with a quadruplet regimen including a proteasome inhibitor (Bortezomib \[V\]), immunomodulatory drug (Lenalidomide \[R\]), dexamethasone \[d\] and anti-CD38 monoclonal antibody (Daratumumab \[D\] or Isatuximab \[Isa\]) followed by anitocabtagene autoleucel. Participants in Cohorts A and B will receive lenalidomide maintenance therapy following infusion with anitocabtagene autoleucel.
Approximately 30 participants will be enrolled to receive induction therapy followed by a single dose of anitocabtagene autoleucel (\~ 10 patients treated at target treatment dose per cohort). Participants will be distributed in 3 cohorts of treatment (A, B and C). Participants of cohort A will be transplant eligible while participants of cohorts B and C will not be planned to receive transplantation: 1. Induction therapy: * Cohort A: will consist of a total of 6 cycles D-VRd (28-day cycles); 3 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 3 additional cycles. * Cohort B: will consist of a total of 4 cycles Isa-VRd (42-day cycles); 2 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 2 additional cycles. * Cohort C: will consist of a total of 4 cycles Isa-VRd (42-day cycles); 2 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 2 additional cycles. 2. Bridging Therapy: Bridging therapy will not be required because the leukapheresis and manufacturing will be planned during the induction phase to allow the availability of anitocabtagene autoleucel at the end of the induction therapy. 3. Lymphodepleting Chemotherapy: Chemotherapy regimen consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day will be administered intravenously (IV) daily for 3 days (Days -5 through -3) before administration of anitocabtagene autoleucel. The fludarabine dose may be adjusted for renal function. Initiation of the 3-day lymphodepleting chemotherapy regimen on Day -7 or Day -6 prior to the anitocabtagene autoleucel infusion on Day +1 is permitted. 4. Anitocabtagene Autoleucel: Treatment consists of a single infusion of anitocabtagene autoleucel administered intravenous (IV) on Day 1 at a target dose of 115 x 10e6 (± 10 x 10e6) CAR+ viable T cells. 5. Maintenance Therapy: Cohorts A and B will receive maintenance therapy which will consist of lenalidomide 10 mg daily (days 1 to 28 of repeated 28-day cycle) for 2 years or until unacceptable toxicity, progression as per IMWG criteria, participant withdrawal of consent, death, or study completion, whichever occurs first. If any of these circumstances occur participant maintenance will end. After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Daratumumab will be administered by subcutaneous (SC) injection.
Isatuximab will be administered IV.
Bortezomib dose will be calculated using the patient's actual body surface area at baseline and will be administered by SC injection.
Lenalidomide will be administered by oral route (all cohorts at induction, and cohorts A and B at maintenance).
As part of lymphodepleting therapy before CAR-T manufacture, administered IV.
As part of lymphodepleting therapy before CAR-T manufacture, administered IV
Single infusion IV
Hospital Germans Trias i Pujol (ICO BADALONA)
Badalona, Spain
RECRUITINGH. Clinic de Barcelona
Barcelona, Spain
RECRUITINGH. 12 de Octubre
Madrid, Spain
RECRUITINGH. Ramón y Cajal
Madrid, Spain
RECRUITINGClinica Universidad de Navarra
Pamplona, Spain
RECRUITINGHospital Clinico Universitario Salamanca
Salamanca, Spain
RECRUITINGH. Marqués de Valdecilla
Santander, Spain
RECRUITINGC H Santiago de Compostela
Santiago de Compostela, Spain
RECRUITINGComplejo Hosp. Regional Virgen del Rocío
Seville, Spain
RECRUITINGHospital Universitario y Politécnico La Fe de Valencia
Valencia, Spain
RECRUITINGIncidence and severity of all adverse events (AEs)
To characterize the safety of anitocabtagene autoleucel following induction therapy (incidence of treatment-emergent adverse events).
Time frame: 3 years
Undetectable minimal residual disease (uMRD) negative-CR rate (minimum 10-5) at 12 months (+/- 3 months) after enrollment.
To further characterize the efficacy profile of anitocabtagene autoleucel following induction therapy. MRD measured by Next Generation Flow Cytometry (NGF, with a sensitivity level of 10-6).
Time frame: 12 months
Undetectable minimal residual disease (MRD) negative CR rate (minimum 10-5) at 2, 6, 12, 18 and 24 months after CAR T infusion and sustained undetectable minimal residual disease (uMRD) annually.
To further characterize the efficacy profile of anitocabtagene autoleucel following induction therapy. MRD measured by Next Generation Flow Cytometry.
Time frame: 2 years
Stringent complete response (sCR) or complete response (CR) rate, as assessed by investigators according to the International Myeloma Working Group (IMWG) criteria.
CR measured by cytomorphplogy and flow cytometry.
Time frame: 6 months
Overall MRD negativity (minimum 10e-5)
MRD measured by Next Generation Flow Cytometry.
Time frame: 3 years
Rate of conversion from undetectable to detectable MRD as well as biochemical progression rate.
MRD measured by Next Generation Flow Cytometry. Biochemical progression by measuring serum and/or urine monoclonal protein alone or with clinical features suggestive of progression including CRAB (C, hypercalcemia; R, renal failure; A, anemia; B, bone disease) symptoms.
Time frame: 3 years
Time to biochemical progression (including the conversion from undetectable to detectable MRD).
MRD measured by Next Generation Flow Cytometry. Serum and/or urine monoclonal protein alone or with clinical features suggestive of progression including CRAB (C, hypercalcemia; R, renal failure; A, anemia; B, bone disease) symptoms.
Time frame: 3 years
Undetectable MRD at 10e-6 (0.0001%)
MRD measured by Next Generation Flow Cytometry. Undetectable MRD at 10e-6 (10 elevated to -6, which is the same as 0.0001%) means no presence of multiple myloma cells within 1,000,000 cells analyzed by flow cytometry
Time frame: 3 years
Overall Response Rate (ORR) per International Myeloma Working Group (IMWG) criteria
ORR is defined as the proportion of participants who achieve a best overall response of at least partial response (PR) or better (sCR, CR, VGPR, or PR) per IMWG criteria.
Time frame: 3 years
Duration of Response (DoR)
DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per IMWG criteria and is defined as the time from first overall response to disease progression per IMWG criteria, or death from any cause, whichever occurs first.
Time frame: 3 years
Progression Free Survival (PFS)
PFS is defined as the time from enrollment to the first documented disease progression per IMWG criteria as determined by investigator assessed or death due to any cause, whichever occurs first.
Time frame: 3 years
Overall survival (OS)
OS is defined as the time from enrollment to the date of death from any cause.
Time frame: 3 years
Overall rate of "imaging plus MRD negative" (using PET/CT per International Myeloma Working Group [IMWG] criteria)
Measured by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan using the Deauville score. The Deauville score is a 5-point grading system used on FDG PET/CT imaging to assess treatment response. It is based on comparing FDG uptake in lesions with uptake in the liver and mediastinum. The Deauville score values are: 1. No FDG uptake above background. 2. Uptake less than the liver. 3. Uptake equal to the liver. 4. Uptake moderately greater than the liver. 5. Uptake markedly greater than the liver, typically 2-3 times greater.
Time frame: 3 years
Expansion and persistence of anitocabtagene autoleucel in peripheral blood
Measured by Next Generation Flow Cytometry.
Time frame: 2.5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.