Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma (GEM-AnitoFIRST)

NCT07045909 | Recruiting Phase 2 FDA Drug

• 1 other identifier: GEM-AnitoFIRST
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

De Novo Multiple Myeloma; Anitocabtagene Autoleucel

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of all adverse events (AEs)

  To characterize the safety of anitocabtagene autoleucel following induction therapy (incidence of treatment-emergent adverse events).

  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).

  12 months

Secondary Outcomes (12)

• 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.

  2 years

• Stringent complete response (sCR) or complete response (CR) rate, as assessed by investigators according to the International Myeloma Working Group (IMWG) criteria.

  6 months

• Overall MRD negativity (minimum 10e-5)

  3 years

• Rate of conversion from undetectable to detectable MRD as well as biochemical progression rate.

  3 years

• Time to biochemical progression (including the conversion from undetectable to detectable MRD).

  3 years

Study Arms (3)

Cohort A

EXPERIMENTAL

Cohort A participants will be transplant eligible. Cohort A participants will receive induction with 6 cycles D-VRd. After induction, lymphodepleting chemotherapy will be administered consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day intravenous (IV) daily for 3 days before administration of anitocabtagene autoleucel. 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. After lymphodepletion, participants will receive a single infusion of anitocabtagene autoleucel administered IV. After CAR T-cell infusion, cohort A participants will receive maintenance therapy with lenalidomide 10 mg daily for 2 years or until unacceptable toxicity, progression as per IMWG criteria, participant withdrawal of consent, death, or study completion, whichever occurs first.

Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anitocabtagene Autoleucel

Cohort B

EXPERIMENTAL

Cohort B participants will not be transplant eligible. Cohort B participants will receive induction with 4 cycles Isa-VRd. After induction, lymphodepleting chemotherapy will be administered consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day IV daily for 3 days before administration of anitocabtagene autoleucel. 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. After lymphodepletion, participants will receive a single infusion of anitocabtagene autoleucel administered IV. After CAR T-cell infusion, cohort B participants will receive maintenance therapy with lenalidomide 10 mg daily for 2 years or until unacceptable toxicity, progression as per IMWG criteria, participant withdrawal of consent, death, or study completion, whichever occurs first.

Drug: Isatuximab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anitocabtagene Autoleucel

Cohort C

EXPERIMENTAL

Cohort C participants will not be transplant eligible. Cohort C participants will receive induction with 4 cycles Isa-VRd; 2 cycles followed by leukapheresis for T-cell collection to manufacture anitocabtagene autoleucel, followed by 2 additional cycles. After induction, lymphodepleting chemotherapy will be administered consisting of cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day 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. After lymphodepletion, participants will receive a single infusion of anitocabtagene autoleucel administered IV with a dose of 115 x 10e6 (± 10 x 10e6) CAR+ viable T cells. After CAR T-cell infusion, cohort C participants will not receive maintenance therapy.

Drug: Isatuximab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anitocabtagene Autoleucel

Interventions

Daratumumab DRUG

Daratumumab will be administered by subcutaneous (SC) injection.

Cohort A

Isatuximab DRUG

Isatuximab will be administered IV.

Cohort B; Cohort C

Bortezomib DRUG

Bortezomib dose will be calculated using the patient's actual body surface area at baseline and will be administered by SC injection.

Cohort A; Cohort B; Cohort C

Lenalidomide DRUG

Lenalidomide will be administered by oral route (all cohorts at induction, and cohorts A and B at maintenance).

Cohort A; Cohort B; Cohort C

Cyclophosphamide DRUG

As part of lymphodepleting therapy before CAR-T manufacture, administered IV.

Cohort A; Cohort B; Cohort C

Fludarabine DRUG

As part of lymphodepleting therapy before CAR-T manufacture, administered IV

Cohort A; Cohort B; Cohort C

Anitocabtagene Autoleucel DRUG

Single infusion IV

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed Multiple Myeloma according to the IMWG criteria published in 2014.
• For cohort A, patients will ≤ 70 years of age.
• For the cohorts B and C, patients will be ≤ 80 years of age.
• Measurable disease at screening per IMWG, defined as any of the following:
• Serum M-protein level ≥ 1 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
• Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio.
• Note: Local laboratory results may be used to establish measurable disease at screening if the results are ≥ 125% of requirements.
• Only participants who are candidates to receive either D-VRd or Isa-VRd induction regimens, as determined by the investigator, should be considered for this study.
• Male or female aged 18 years or older and has capacity to give informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematological function defined as the following:
• Hemoglobin count ≥ 7.5 g/dL (without any red blood cell \[RBC\] transfusion within 7 days prior to the test result; use of recombinant human erythropoietin is permitted).
• Absolute neutrophil count (ANC) ≥ 500/μL (without non-PEGylated myeloid growth factor support within 7 days or PEGylated myeloid growth factor support within 14 days prior to the test result).
• Platelet count ≥ 75,000/μL (unless secondary to bone marrow or spleen involvement of MM, in which platelet count ≥ 50,000/μL is permitted) without any platelet cell transfusion within 7 days prior to the test result. Bone marrow involvement by MM is demonstrated by bone marrow aspiration or biopsy. Spleen involvement by MM is demonstrated by splenomegaly.
• Absolute lymphocyte count (ALC) ≥ 100/μL.

You may not qualify if:

• Active or prior history of central nervous system (CNS) or meningeal involvement of MM.
• Cardiac atrial or cardiac ventricular MM involvement.
• Diagnosis of primary amyloidosis (AL), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia (PCL), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or Waldenstrom's macroglobulinemia at the time of screening.
• Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted. Allowed malignancy exceptions are:
• Localized skin cancer (melanoma and nonmelanoma) that has been completely resected and considered curative within the last 24 months is eligible.
• Cervix carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible.
• Bladder carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible.
• Breast carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible. Hormonal therapy after curative-intent treatment is permitted.
• Prostate cancer that is low grade and localized (Grade Group 1, has not spread to nearby lymph nodes \[N0\] or metastasized \[M0\]) within the last 24 months is eligible, including cases under surveillance only as part of standard of care. Androgen deprivation therapy is permitted.
• Localized renal cell carcinoma (≤ Stage 2) that has been completely resected and considered curative within the last 24 months is eligible.
• Localized (Stage 1) colorectal cancer that has been completely resected and considered curative (without need for adjuvant chemotherapy) within the last 24 months is eligible.
• Any prior systemic anti-myeloma treatment (including BCMA-directed treatment) and/or radiotherapy before enrollment. Palliative radiation and corticosteroids (up to cumulative dose of 160mg prednisone or equivalent, and not requiring ongoing therapy) prior to enrollment are permitted. Participants must have recovered from all radiation-related toxicities. Patients with radiation-induced lung injury (RILI, radiation pneumonitis) during screening are excluded.
• Prior allogeneic stem cell transplant (allo-SCT) (even if for another malignancy)
• Live vaccine ≤ 4 weeks before enrollment and/or anticipating needing the vaccine during study period.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is systemic uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if the participant is responding to active treatment and satisfies the criteria of being afebrile (i.e., temperature \< 38°C) for at least 24 hours prior to the investigator confirming the participant's eligibility.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (10)

Hospital Germans Trias i Pujol (ICO BADALONA)

Badalona, Spain

RECRUITING

H. Clinic de Barcelona

Barcelona, Spain

RECRUITING

H. 12 de Octubre

Madrid, Spain

RECRUITING

H. Ramón y Cajal

Madrid, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Spain

RECRUITING

Hospital Clinico Universitario Salamanca

Salamanca, 37007, Spain

RECRUITING

H. Marqués de Valdecilla

Santander, Spain

RECRUITING

C H Santiago de Compostela

Santiago de Compostela, Spain

RECRUITING

Complejo Hosp. Regional Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, Spain

RECRUITING

MeSH Terms

Interventions

daratumumab; isatuximab; Bortezomib; Lenalidomide; Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• María Victoria Mateos, MD PhD

  Hospital Universitario de Salamanca (Salamanca)

  PRINCIPAL INVESTIGATOR

• Jesús San Miguel, Professor

  Clínica Universidad de Navarra (Pamplona)

  STUDY DIRECTOR

• Juan José Lahuerta, MD PhD

  Hospital Universitario 12 de Octubre (Madrid)

  STUDY CHAIR

• Joan Bladé, MD PhD

  Hospital Clínic i Provincial de Barcelona (Barcelona)

  STUDY CHAIR

Central Study Contacts

Carmen López-Carrero

CONTACT

0034 699 835 437; carmen@fundacionpethema.es

Roberto Maldonado

CONTACT

0034 683 15 66 87; roberto.maldonado@fundacionpethema.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, open-label, multicenter multicohort trial

Study Record Dates

• First Submitted: June 22, 2025
• First Posted: July 1, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2030
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

ES (10)