ZAMTOCABTAGENE AUTOLEUCEL for Relapsed/refractory mature B-cell neoplasms | B-cell lymphoma

Inclusion criteria

• {"criterion_text":"- 1.Subjects must meet all the following inclusion criteria to be eligible for inclusion in this study: Is able to provide age-appropriate assent/consent (as applicable, according to local legislation) and/or have a guardian able to provide consent signed and dated by the parent(s) or by subject’s legal guardian before conduct of any study-specific procedures."}
• {"criterion_text":"- 7.\tTissue samples archival or fresh (preferred) from recent relapse or initial diagnosis (in case of primary refractory disease) must be made available for the central pathology review to confirm diagnosis (≤2 years, preferably not older than 2 months since collection)."}
• {"criterion_text":"- 8.\tHas Karnofsky (aged ≥16 years) or Lansky (aged <16 years) performance status ≥60."}
• {"criterion_text":"- 9.\tHas adequate bone marrow function as defined by the following laboratory values (as assessed by local laboratory for eligibility): o\tAbsolute neutrophil count (ANC) >1000/µL. o\tPlatelets ≥50000/µL. o\tHemoglobin ≥8.0 g/dL. o\tAbsolute lymphocyte count ≥100/µL."}
• {"criterion_text":"- 13.\tIs willing to undergo collection of non-mobilized leukapheresis."}
• {"criterion_text":"- 14.\tIn the opinion of the investigator, the subject must be able to comply with all study related procedures, medication use, and assessments."}
• {"criterion_text":"- 10.\tHas adequate organ function as follows: o\tRenal function: estimated glomerular filtration rate (eGFR) >29 mL/min by Schwartz formula (Schwartz et al 1976). o\tAspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × upper limit of normal (ULN) for age. o\tBilirubin <1.5 x ULN (for Gilbert’s Syndrome, subject’s total bilirubin <4 mg/dL). o\tAdequate pulmonary function as follows: -\tResting oxygen saturation of ≥91% on room air. -\tNo or mild dyspnea (Grade ≤1).\""}
• {"criterion_text":"- 11.\tFemale subjects of childbearing potential must be willing to undergo pregnancy tests before MB-CART2019.1 infusion."}
• {"criterion_text":"- 12.\tIf subjects are sexually active, they must be willing to use highly effective methods of contraception. o\tFemale subjects must agree to use two methods of contraception; -\tone of the following methods (Pearl index <1%): Hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, injected, implanted, transdermal), intrauterine devices (IUDs) or systems (e.g., hormonal and non-hormonal IUD), or vasectomized sexual partner AND one barrier method. -\tHighly effective methods of contraception must be followed from inclusion until 12 months after MB-CART2019.1 infusion. o\tMale subjects must agree to use a condom during intercourse from inclusion through at least 12 months after MB-CART2019.1 infusion to prevent them from fathering a child AND to prevent delivery of MB-CART2019.1 via seminal fluid to their partner. Do not use a female condom when using a male condom, since tearing can occur. In addition, male subjects must not donate sperm for the time period specified above. o\tFemales must agree not to breast feed or donate eggs/ova during the study and until at least 12 months after MB-CART2019.1 infusion."}
• {"criterion_text":"- 2.\tHas histologically confirmed mature CD19+ and/or CD20+ B-cell neoplasm according to the WHO 2022 classification of hematolymphoid tumors such as:o\tBurkitt lymphoma/Burkitt leukemia o\tDiffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) o\tPrimary mediastinal (thymic) large B-cell lymphoma o\tBurkitt-like lymphoma with 11q aberration o\tAggressive mature B-cell lymphoma o\tOther rare aggressive B-cell non-Hodgkin lymphoma (NHL) after sponsor approval.\""}
• {"criterion_text":"- 3.\tHas r/r B-cell neoplasms after one or more prior therapies or primary refractory to first-line therapy.Patients must have received adequate standard combination chemotherapy containing at least one anthracycline and/or methotrexate. Local therapies (e.g. radiotherapy) will not be considered a line of therapy if they are performed during the same line of treatment. Subjects who previously failed to respond to approved anti-CD19 or anti-CD20 CAR-T cell therapies will be permitted to participate in the study."}
• {"criterion_text":"- 4.\tIs a pediatric/adolescent (aged between 6 months and <18 years)."}
• {"criterion_text":"- 5.\tHas a BW of ≥ 6 kg."}
• {"criterion_text":"- 6.\tMeasurable disease based on the International Pediatric NHL Response Criteria (which refers to the Lugano criteria for definitions of measurability and selecting index lesions), as identified by local radiological assessment for lymphomas. Previously irradiated lesions cannot be considered measurable unless the lesion has proven radiological evidence for progression after the radiation."}

Exclusion criteria

• {"criterion_text":"- 1. Is receiving active treatment for malignant disease (including participation in any additional parallel investigational drug or device studies), except for pre-enrollment therapy, including radiotherapy. Lesions that are irradiated during pre-enrollment therapy may not be considered measurable lesions. For subjects with lymphoma to be eligible, there must be at least one measurable lesion after pre-enrollment therapy."}
• {"criterion_text":"- 10. Presence of active or prior hepatitis B or C as indicated by serology. Treated infection with hepatitis B or C virus unless confirmed to be polymerase chain reaction (PCR) negative."}
• {"criterion_text":"- 11.\tHas infection with Treponema pallidum."}
• {"criterion_text":"- 12. Has active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2)."}
• {"criterion_text":"- 13.\tHas infection with human T-lymphotropic virus 1/2 (HTLV 1/2)."}
• {"criterion_text":"- 14.Has active severe systemic fungal, viral, or bacterial infection, requiring systemic antiviral, antifungal, or antimicrobial therapy."}
• {"criterion_text":"- 15. Has clinically significant seizures according to the opinion of by the investigator."}
• {"criterion_text":"- 16.\tHas history of cerebral vascular accident within 12 months prior to leukapheresis."}
• {"criterion_text":"- 17. Has impaired cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography or multigated acquisition, if allowed as per local law."}
• {"criterion_text":"- 18. Has concomitant genetic syndromes associated with bone marrow (BM) failure status, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known BM failure syndrome."}
• {"criterion_text":"- 19. Is a pregnant or breast-feeding female."}
• {"criterion_text":"- 2.Had allogeneic HSCT."}
• {"criterion_text":"- 20. Is sexually active and not willing to use highly effective methods of contraception as described in the inclusion criteria."}
• {"criterion_text":"- 21.\tHas history of another malignancy within the prior 3 years that required systemic therapy."}
• {"criterion_text":"- 22.\tHas other medical, psychological, or social condition that, in the opinion of the investigator, would impact subject safety or confound the study results."}
• {"criterion_text":"- 23.\tHas received vaccination with live virus within 6 weeks prior to informed consent/assent."}
• {"criterion_text":"- 24.\tHas been previously treated with approved anti-CD19 or anti-CD20 CAR-T cell therapies <100 days prior to informed consent/assent."}
• {"criterion_text":"- 3.Had autologous HSCT <120 days prior to written informed consent/assent."}
• {"criterion_text":"- 4.Had major surgery within 2 weeks before leukapheresis, or has not fully recovered from an earlier surgery, or has major surgery planned during the time the subject is expected to participate in the study."}
• {"criterion_text":"- 5.Subjects with B-cell neoplasms in the context of post-transplant lymphoproliferative disorders-associated lymphomas."}
• {"criterion_text":"- 6.Has known hypersensitivity to the excipients of the MB-CART2019.1 or to any other drug product as advised for administration in the study protocol (e.g., lymphodepleting agents)."}
• {"criterion_text":"- 7.Has active central nervous system (CNS) involvement at the time point of eligibility confirmation, as measured by the presence of lymphoma cells in cerebral spinal fluid (CSF) on cytospin preparation."}
• {"criterion_text":"- 8. Has history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory diseases."}
• {"criterion_text":"- 9. Infection with human immunodeficiency virus (HIV)."}

Primary endpoints

• {"endpoint_text":"- •\tType, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). Primary efficacy estimand:","definition_or_measurement_approach":"Safety assessed by recording type, frequency and severity of AEs, SAEs and AESIs; primary efficacy estimand text not further specified in record."}
• {"endpoint_text":"- BORR, defined as the proportion of subjects with at least one partial response (PR) or complete response (CR) based on independent review committee (IRC) assessment from MB-CART2019.1 infusion until progressive disease (PD), start of new anti lymphoma therapy, lost to follow-up or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"BORR measured as proportion of subjects with ≥1 PR or CR by IRC assessment from infusion until PD, start of new anti-lymphoma therapy, loss to follow-up, or death (whichever first)."}

Secondary endpoints

• {"endpoint_text":"- Key secondary efficacy endpoints •\tBORR until Week 24, defined as the proportion of subjects with at least one PR or CR after the MB-CART2019.1 infusion, based on IRC assessment until Week 24.","definition_or_measurement_approach":"BORR until Week 24 by IRC assessment."}
• {"endpoint_text":"- •\tCRR, defined as the proportion of subjects with at least one CR assessment, based on IRC assessment. \"","definition_or_measurement_approach":"CRR proportion with ≥1 CR by IRC assessment."}
• {"endpoint_text":"- •\tDOR, defined as the time between the date of first objective response (CR/PR) until the date of PD, based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. \"","definition_or_measurement_approach":"DOR = time from first objective response (CR/PR) to PD, loss to follow-up, or death (IRC assessment)."}
• {"endpoint_text":"- •\tDOCR, defined as the time between the date of first CR until the date of PD, based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. \"","definition_or_measurement_approach":"DOCR = time from first CR to PD, loss to follow-up, or death (IRC assessment)."}
• {"endpoint_text":"- •\tTTR, defined as the time between the date of MB-CART2019.1 infusion and the date of a first objective response (CR/PR), based on IRC assessment. \"","definition_or_measurement_approach":"TTR = time from infusion to first objective response (CR/PR) by IRC."}
• {"endpoint_text":"- •\tTTCR, defined as the time between the date of MB-CART2019.1 infusion and the date of a first objective CR, based on IRC assessment. \"","definition_or_measurement_approach":"TTCR = time from infusion to first objective CR by IRC."}
• {"endpoint_text":"- •\tORR, defined as the proportion of subjects with a PR or CR, based on IRC assessment, at the following visits: Day 28, Week 8, Week 12, Week 24, Week 52, and Week 78. \"","definition_or_measurement_approach":"ORR measured at specified visits (Day 28, Weeks 8,12,24,52,78) by IRC assessment."}
• {"endpoint_text":"- •\tEFS, defined as the time between the date of the MB-CART2019.1 infusion and the date of an event (PD, start of a new anti-lymphoma therapy after MB-CART2019.1 infusion excluding hematopoietic stem cell transplantation [HSCT], relapse, or death due to any cause), based on IRC assessment. \"","definition_or_measurement_approach":"EFS = time from infusion to event (PD, start new anti-lymphoma therapy excluding HSCT, relapse, or death) by IRC."}
• {"endpoint_text":"- •\tPFS, defined as the time between the date of MB-CART2019.1 infusion and the date of PD based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. \"","definition_or_measurement_approach":"PFS = time from infusion to PD, loss to follow-up, or death (IRC assessment)."}
• {"endpoint_text":"- •\tOS, defined as the time between the date of MB-CART2019.1 infusion and the date of death due to any cause, irrespective of new anti-lymphoma therapy. \"","definition_or_measurement_approach":"OS = time from infusion to death from any cause."}
• {"endpoint_text":"- •\tOS rates at Week 52 and at Week 78. \"","definition_or_measurement_approach":"OS rates assessed at Week 52 and Week 78."}
• {"endpoint_text":"- • BORR, based on investigator assessment. \"","definition_or_measurement_approach":"BORR assessed by investigator (as alternative to IRC)."}
• {"endpoint_text":"- • BORR until Week 24, based on investigator assessment. \"","definition_or_measurement_approach":"BORR until Week 24 by investigator assessment."}
• {"endpoint_text":"- • CRR, based on investigator assessment. \"","definition_or_measurement_approach":"CRR by investigator assessment."}
• {"endpoint_text":"- • DOR, based on investigator assessment. \"","definition_or_measurement_approach":"DOR by investigator assessment."}
• {"endpoint_text":"- • DOCR, based on investigator assessment.","definition_or_measurement_approach":"DOCR by investigator assessment."}
• {"endpoint_text":"- • TTR, based on investigator assessment. \"","definition_or_measurement_approach":"TTR by investigator assessment."}
• {"endpoint_text":"- • TTCR, based on investigator assessment. \"","definition_or_measurement_approach":"TTCR by investigator assessment."}
• {"endpoint_text":"- • ORR, based on investigator assessment, at the following visits: Day 28, Week 8, Week 12, Week 24, Week 52, and Week 78. \"","definition_or_measurement_approach":"ORR by investigator at listed visits."}
• {"endpoint_text":"- • EFS, based on investigator assessment. \"","definition_or_measurement_approach":"EFS by investigator assessment."}
• {"endpoint_text":"- • PFS, based on investigator assessment.","definition_or_measurement_approach":"PFS by investigator assessment."}
• {"endpoint_text":"- • Occurrence and persistence of B-cell aplasia. \"","definition_or_measurement_approach":"Occurrence and persistence of B-cell aplasia measured (method not further specified)."}
• {"endpoint_text":"- • The proportion of subjects who proceed to HSCT after MB-CART2019.1 infusion until end of study (EOS). \"","definition_or_measurement_approach":"Proportion proceeding to HSCT after infusion until EOS."}
• {"endpoint_text":"- • Types and levels of cytokines (including soluble interleukin-2 receptor [sIL-2R], IL-6, IL-10, IL-15, interferon gamma [IFN-γ], and tumor necrosis factor alpha [TNF-α])","definition_or_measurement_approach":"Cytokine types/levels measured (assays not further specified)."}
• {"endpoint_text":"- • Persistence and phenotype of MB-CART2019.1, based on flow cytometry analyses and persistence based on quantitative polymerase chain reaction (qPCR). \"","definition_or_measurement_approach":"Persistence/phenotype measured by flow cytometry and qPCR."}
• {"endpoint_text":"- • Anti-MB-CART2019.1 antibody via anti-drug antibody assay \"","definition_or_measurement_approach":"Anti-drug antibodies assessed via ADA assay."}
• {"endpoint_text":"- • Change from baseline in HRQoL, using the EuroQol-5 Dimensions-Youth (EQ-5D-Y) questionnaire\"","definition_or_measurement_approach":"HRQoL change measured by EQ-5D-Y questionnaire."}
• {"endpoint_text":"- • Hospital days within 6 months after MB-CART2019.1 infusion. \"","definition_or_measurement_approach":"Number of hospital days within 6 months after infusion."}
• {"endpoint_text":"- • Intensive care unit (ICU) admission days within 6 months after MB-CART2019.1 infusion. \"","definition_or_measurement_approach":"ICU admission days within 6 months after infusion."}
• {"endpoint_text":"- • Use of tocilizumab and/or high-dose steroids and/or anti-interleukin medication. \"","definition_or_measurement_approach":"Use of rescue/management medications recorded."}
• {"endpoint_text":"- • Need for transfusions, prophylactic antimicrobial therapy, and gamma globulin substitution within 12 months after MB-CART2019.1 infusion.","definition_or_measurement_approach":"Occurrence of transfusions, prophylactic antimicrobials, gamma globulin substitution within 12 months recorded."}
• {"endpoint_text":"- • Change in clinical laboratory assessments, physical and neurological examinations, and electrocardiogram (ECG) parameters within 6 months after MB-CART2019.1 infusion. \"","definition_or_measurement_approach":"Changes in labs, physical/neurological exams and ECG parameters within 6 months monitored."}
• {"endpoint_text":"- • Monitoring of RCL by qPCR\"","definition_or_measurement_approach":"Replication-competent lentivirus monitored by qPCR."}
• {"endpoint_text":"- • CD19/CD20 antigen expression in tumor biopsies in case of relapse after MB-CART2019.1 infusion","definition_or_measurement_approach":"CD19/CD20 expression in tumor biopsies assessed at relapse."}

Germany

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

525

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

570

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

534

Number Of Sites

2

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

525

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Miltenyi Biomedicine GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"SCRATCH Pharmacovigilance GmbH & Co. KG","duties_or_roles":"codes: 13; 15 (Medical monitoring service)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"spm²-safety projects & more GmbH","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"codes: 1, 11, 12, 15 (Pharmacovigilance ( SUSAR cross reporting to sites)), 2, 3, 5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Mlm Medical Labs GmbH","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"EvidentlQ Germany GmbH","duties_or_roles":"code: 15 (Software Vendor)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Stichting EuroQol Research Foundation","duties_or_roles":"code: 15 (PRO vendor)","organisation_type":"Patient organisation/association"}
• {"country":"Germany","full_name":"Miltenyi Biotec B.V. & Co. KG","duties_or_roles":"code: 15 (Investigational Medicinal Product Manufacturer)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Julius-Maximilians-Universitaet Wuerzburg","duties_or_roles":"code: 4","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"code: 15 (Patient Transportation / Reimbursement)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Miltenyi Biotec B.V. & Co. KG","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}