Zamtocabtagene autoleucel (MB-CART2019.1) for children and teens with relapsed or refractory mature B‑cell cancers

A Single-arm, Multi-center, Open-label Phase II Study to Determine the Safety and Efficacy of MB-CART2019.1 in Pediatric Subjects With Relapsed/Refractory Mature B-cell Neoplasms Who Have Relapsed After One or More Prior Therapies, Including Subjects With Primary Refractory Disease

This study will try one fresh infusion of MB-CART2019.1, a tandem CD20‑CD19 CAR‑T treatment, in children and adolescents (6 months to under 18 years) whose mature B‑cell cancers have come back or not responded to prior therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Ages: 6 Months to 17 Years
• Sex: All
• Sponsor: Miltenyi Biomedicine GmbH (Industry-sponsored)
• Drugs / interventions: CART, radiation, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 5 sites (Paris, Boulevard Sérurier 48 and 4 other locations)
• Trial ID: NCT06508931 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, multicenter, open‑label Phase II trial giving eligible pediatric patients a single fresh infusion of zamtocabtagene autoleucel (MB‑CART2019.1) after lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Patients undergo leukapheresis to collect autologous T cells, manufacturing of a tandem CD20‑CD19 CAR‑T product, and administration at a target dose of 2.5 × 10^6 CAR‑transduced T cells per kg bodyweight. The primary endpoint is best overall response rate (BORR), and safety is monitored by tracking adverse events, serious adverse events, and adverse events of special interest during a 78‑week safety follow‑up. Enrollment is planned over about 36 months and each participant is followed for a total of 85 weeks including screening.

Who should consider this trial

Good fit: Children and adolescents aged 6 months to under 18 years, weighing at least 6 kg, with measurable relapsed or refractory mature CD19+ and/or CD20+ B‑cell neoplasms who can undergo leukapheresis and lymphodepleting chemotherapy.

Not a fit: Patients whose tumors lack CD19 or CD20 expression, who cannot tolerate leukapheresis or lymphodepletion, or who have severe organ dysfunction or uncontrolled infections are unlikely to benefit.

Why it matters

Potential benefit: If successful, the therapy could produce meaningful and possibly durable remissions in children whose B‑cell cancers have returned or not responded to other treatments.

How similar studies have performed: CD19‑targeted CAR‑T therapies have produced strong remissions in pediatric B‑cell malignancies, though the tandem CD20‑CD19 approach and the fresh, non‑cryopreserved product used here are less widely tested.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Has histologically confirmed mature CD19+ and/or CD20+ B-cell neoplasm such as:

   * Burkitt lymphoma/Burkitt leukemia
   * Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
   * Primary mediastinal (thymic) large B-cell lymphoma
   * Burkitt-like lymphoma with 11q aberration
   * Aggressive mature B-cell lymphoma
   * Other rare aggressive B-cell non-Hodgkin lymphoma (NHL) after sponsor approval.
3. Has r/r B-cell neoplasms after one or more prior therapies or primary refractory to first-line therapy.
4. Is a pediatric/adolescent (aged between 6 months and \<18 years).
5. Has a BW of ≥ 6 kg.
6. Measurable 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.
7. Tissue 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).
8. Has Karnofsky (aged ≥16 years) or Lansky (aged \<16 years) performance status ≥60.
9. Has adequate bone marrow function as defined by the following laboratory values (as assessed by local laboratory for eligibility):

   * Absolute neutrophil count (ANC) \>1000/μL.
   * Platelets ≥50000/μL.
   * Hemoglobin ≥8.0 g/dL.
   * Absolute lymphocyte count ≥100/μL.
10. Has adequate organ function as follows:

    * Renal function: estimated glomerular filtration rate (eGFR) \>29 mL/min by Schwartz formula (Schwartz et al 1976).
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × upper limit of normal (ULN) for age.
    * Bilirubin \<1.5 x ULN (for Gilbert's Syndrome, subject's total bilirubin \<4 mg/dL).
    * Adequate pulmonary function as follows:

      * Resting oxygen saturation of ≥91% on room air.
      * No or mild dyspnea (Grade ≤1).
11. Female subjects of childbearing potential must be willing to undergo pregnancy tests before MB-CART2019.1 infusion.
12. If subjects are sexually active, they must be willing to use highly effective methods of contraception.

    * Female subjects must agree to use two methods of contraception;

      * one 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.
      * Highly effective methods of contraception must be followed from inclusion until 12 months after MB-CART2019.1 infusion.
    * Male 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.
    * Females must agree not to breast feed or donate eggs/ova during the study and until at least 12 months after MB-CART2019.1 infusion.
13. Is willing to undergo collection of non-mobilized leukapheresis.
14. In the opinion of the investigator, the subject must be able to comply with all study-related procedures, medication use, and assessments.

Exclusion Criteria:

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.
2. Had allogeneic HSCT.
3. Had autologous HSCT \<120 days prior to written informed consent.
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.
5. Subjects with B-cell neoplasms in the context of post-transplant lymphoproliferative disorders-associated lymphomas.
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).
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.
8. Has history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory diseases.
9. Infection with human immunodeficiency virus (HIV).
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.
11. Has infection with Treponema pallidum.
12. Has active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
13. Has infection with human T-lymphotropic virus 1/2 (HTLV 1/2).
14. Has active severe systemic fungal, viral, or bacterial infection, requiring systemic antiviral, antifungal, or antimicrobial therapy.
15. Has clinically significant seizures according to the opinion of by the investigator.
16. Has history of cerebral vascular accident within 12 months prior to leukapheresis.
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.
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.
19. Is a pregnant or breast-feeding female.
20. Is sexually active and not willing to use highly effective methods of contraception as described in the inclusion criteria.
21. Has history of another malignancy within the prior 3 years that required systemic therapy.
22. Has other medical, psychological, or social condition that, in the opinion of the investigator, would impact subject safety or confound the study results.
23. Has received vaccination with live virus within 6 weeks prior to informed consent.
24. Has been previously treated with approved anti-CD19 or anti-CD20 CART cell therapies \<100 days prior to informed consent/assent.

Where this trial is running

Paris, Boulevard Sérurier 48 and 4 other locations

• Hôpital Robert Debré — Paris, Boulevard Sérurier 48, France (Active_not_recruiting)
• Institut Gustave Roussy — Villejuif, France (Recruiting)
• Universitaetsklinikum Muenster (UKM) - Klinik fuer Kinder- und Jugendmedizin - Paediatrische Haematologie und Onkologie — Münster, Albert-Schweitzer-Campus 1, Gebaeude A1, Germany (Active_not_recruiting)
• IRCCS Ospedale Pediatrico Bambino Gesù — Rome, Piazza Sant Onofrio 4, Italy (Recruiting)
• Prinses Maxima Centrum — Utrecht, Heidelberglaan 25, Netherlands (Active_not_recruiting)

Study contacts

• Principal investigator: Birgit Burkhardt, Prof. Dr. — Uniklinik Münster, Klinik für Kinder- und Jugendmedizin Pädiatrische Hämatologie/Onkologie
• Study coordinator: Andrey Shirokov

Conditions B-Cell Neoplasm