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

NCT ID: NCT07045909

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2030-03-31

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.

Detailed Description

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.

Conditions

De Novo Multiple Myeloma; Anitocabtagene Autoleucel

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

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.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

Daratumumab will be administered by subcutaneous (SC) injection.

Bortezomib

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Anitocabtagene Autoleucel

Intervention Type: DRUG

Single infusion IV

Cohort B

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.

Group Type: EXPERIMENTAL

Isatuximab

Intervention Type: DRUG

Isatuximab will be administered IV.

Bortezomib

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Anitocabtagene Autoleucel

Intervention Type: DRUG

Single infusion IV

Cohort C

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.

Group Type: EXPERIMENTAL

Isatuximab

Intervention Type: DRUG

Isatuximab will be administered IV.

Bortezomib

Intervention Type: DRUG

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

Lenalidomide

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Anitocabtagene Autoleucel

Intervention Type: DRUG

Single infusion IV

Interventions

Daratumumab

Daratumumab will be administered by subcutaneous (SC) injection.

Intervention Type: DRUG

Isatuximab

Isatuximab will be administered IV.

Intervention Type: DRUG

Bortezomib

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

Intervention Type: DRUG

Lenalidomide

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Anitocabtagene Autoleucel

Single infusion IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Newly diagnosed Multiple Myeloma according to the IMWG criteria published in 2014.

1. For cohort A, patients will ≤ 70 years of age.

2. For the cohorts B and C, patients will be ≤ 80 years of age.

2. Measurable disease at screening per IMWG, defined as any of the following:

1. Serum M-protein level ≥ 1 g/dL or urine M-protein level ≥ 200 mg/24 hours; or

2. 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.

3. 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.

4. Male or female aged 18 years or older and has capacity to give informed consent.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. 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.
• PTT/PT/INR < 1.5x upper limit of normal (ULN), unless on a stable dose of anticoagulant for a thromboembolic even (subjects with a history of thromboembolic stroke or history of Grade 2 or greater hemorrhage within 1 year are excluded.

7. Adequate renal, hepatic, pulmonary, and cardiac function defined as the following:

• Estimated glomerular filtration rate (eGFR) (as estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation [Section 12.14]) ≥ 45 mL/min.
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
• Total bilirubin ≤ 1.5 mg/dL, except in participants with Gilbert's syndrome or documented MM liver or pancreatic involvement where ≤ 3 x ULN is permitted.
• Cardiac ejection fraction ≥ 45% with no evidence of clinically significant pericardial effusion as determined by echocardiogram (ECHO). Multigated acquisition (MUGA) scan may be used if an ECHO is not available at the site.
• No evidence of Grade 2 or higher (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) pleural effusion or ascites (participants with Grade 1 pleural effusion or ascites are eligible).
• Baseline oxygen saturation >92% on room air.

8. Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential; refer to Section 12.2).

9. Willing to comply with and able to tolerate study procedures, including consent to participate in separate Long-term Safety Follow-up lasting up to 15 years per authorities´ guidance.

Exclusion Criteria

1. Active or prior history of central nervous system (CNS) or meningeal involvement of MM.

2. Cardiac atrial or cardiac ventricular MM involvement.

3. 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.

4. 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:

1. Localized skin cancer (melanoma and nonmelanoma) that has been completely resected and considered curative within the last 24 months is eligible.

2. Cervix carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible.

3. Bladder carcinoma in situ that has been completely resected and considered curative within the last 24 months is eligible.

4. 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.

5. 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.

6. Localized renal cell carcinoma (≤ Stage 2) that has been completely resected and considered curative within the last 24 months is eligible.

7. 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.

5. 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.

6. Prior allogeneic stem cell transplant (allo-SCT) (even if for another malignancy)

7. Live vaccine ≤ 4 weeks before enrollment and/or anticipating needing the vaccine during study period.

8. 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.

9. Acute or chronic active hepatitis A, B, or C infection. Participants with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines.

10. Human immunodeficiency virus (HIV)-seropositive.

11. Participants with history or presence of chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal will not be permitted to receive anti-CD38 monoclonal antibody in combination with VRd therapy; Note: FEV1 testing is required for participants who are planned

12. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months before enrollment.

a. History or presence of intracranial or CNS disorder, such as hemorrhage, dementia, altered mental status, cerebellar disease, or any autoimmune disease with CNS involvement, PRES, or cerebral edema with confirmed structural defects by appropriate imaging. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication. Patient with history of neurodegenerative disease (e.g., Parkinson's or Alzheimer's disease) must be excluded.

13. Peripheral neuropathy of Grade 3 or higher (per CTCAE v5.0; participants with Grade 2 peripheral neuropathy are eligible).

14. History of solitary plasmacytoma

15. History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in or requiring systemic immunosuppression or systemic disease-modifying agents within 2 years.

16. History of concomitant genetic syndrome associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome.

17. History of DVT or PE within 6 months before enrollment. Anticoagulants (e.g., warfarin, low-molecular weight heparin, Factor Xa inhibitors) are allowed if DVT/PE occurred > 6 months before enrollment, and if the participant is on a stable maintenance dose.

18. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J tube, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.

19. Major surgery within 28 days before enrollment, or planned surgery required during study participation.

20. Any medical, neurologic or psychiatric condition that in the investigator's opinion is likely to interfere with study procedures including assessment of safety or efficacy of the study treatment.

21. Females who are pregnant or breastfeeding (due to the potentially dangerous effects of the lymphodepleting chemotherapy or induction regimen on the fetus or infant).

22. Participants of both sexes who are not willing to practice highly effective birth control from the time of consent through 12 months following lymphodepleting chemotherapy administration, 12 months after the completion of anitocabtagene autoleucel, 5 months after the last dose of isatuximab, 3 months after the last dose of daratumumab, bortezomib, or 28 days after the last dose of lenalidomide, whichever is longer (refer to Section 12.2). Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential. Participants of both sexes must also comply with any relevant REMS or aRMMs as part of an RMP. Additional information is in Section 6.3.1.

23. As per the investigator's judgment, the participant is unlikely to complete all protocol required study visits or procedures, including follow-up visits, or comply with or tolerate the study requirements for participation (e.g., participants who are at a risk for a thromboembolic event and are not willing to take venous thromboembolism prophylaxis should be excluded).

24. Contraindication to fludarabine or cyclophosphamide.

25. History of allergy or hypersensitivity to any study agent or study drug components. Participants with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PETHEMA Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

María Victoria Mateos, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de Salamanca (Salamanca)

Jesús San Miguel, Professor

Role: STUDY_DIRECTOR

Clínica Universidad de Navarra (Pamplona)

Juan José Lahuerta, MD PhD

Role: STUDY_CHAIR

Hospital Universitario 12 de Octubre (Madrid)

Joan Bladé, MD PhD

Role: STUDY_CHAIR

Hospital Clínic i Provincial de Barcelona (Barcelona)

Locations

Hospital Germans Trias i Pujol (ICO BADALONA)

Badalona, , Spain

Site Status: RECRUITING

H. Clinic de Barcelona

Barcelona, , Spain

Site Status: RECRUITING

H. 12 de Octubre

Madrid, , Spain

Site Status: RECRUITING

H. Ramón y Cajal

Madrid, , Spain

Site Status: RECRUITING

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status: RECRUITING

Hospital Clinico Universitario Salamanca

Salamanca, , Spain

Site Status: RECRUITING

H. Marqués de Valdecilla

Santander, , Spain

Site Status: RECRUITING

C H Santiago de Compostela

Santiago de Compostela, , Spain

Site Status: RECRUITING

Complejo Hosp. Regional Virgen del Rocío

Seville, , Spain

Site Status: RECRUITING

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Carmen López-Carrero

Role: CONTACT

carmen@fundacionpethema.es

0034 699 835 437

Roberto Maldonado

Role: CONTACT

roberto.maldonado@fundacionpethema.es

0034 683 15 66 87

Facility Contacts

Albert Oriol Rocafiguera

Role: primary

Ana Triguero

Role: primary

Juan Jose Lahuerta, Dr

Role: primary

jjlahuerta@telefonica.net

J Valentín García Gutiérrez, Dr

Role: primary

jvalentingg@gmail.com

Paula Rodríguez

Role: primary

Mª Victoria Mateos, Dr

Role: primary

mvmateos@usal.es

Arancha Bermúdez

Role: primary

Natalia Alonso, Dr

Role: primary

natalia.alonso.vence@sergas.es

José González Campos, Dr

Role: primary

Javier de la Rubia Comos

Role: primary

Other Identifiers

GEM-AnitoFIRST

Identifier Type: -

Identifier Source: org_study_id