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
Overview
- Phase
- Phase 2
- Intervention
- zamtocabtagene autoleucel (MB-CART2019.1)
- Conditions
- B-Cell Neoplasm
- Sponsor
- Miltenyi Biomedicine GmbH
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) [Safety and toxicity of the study product]
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a single-arm, multi-center, open-label Phase II study to determine the safety and efficacy of MB-CART2019.1 in pediatric and adolescent subjects (aged between 6 months and <18 years, ≥6 kg body weight [BW]) with mature B-cell neoplasms and aggressive lymphomas that relapsed after or are refractory to one or more prior therapies, including subjects with primary refractory disease.
Detailed Description
This is a single-arm, multi-center, open-label Phase II study designed to evaluate the efficacy of zamtocabtagene autoleucel (MB-CART2019.1) therapy infusion in pediatric subjects with relapsed/refractory (r/r) mature B-cell neoplasms. The primary study endpoint will be best overall response (BORR). Furthermore, the safety and toxicity of the study product will be assessed based on type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). MB-CART2019.1 is designed to effectively target malignant B cells in patients suffering from haematological B-cell malignancies. Zamtocabtagene autoleucel (MB-CART2019.1) is a tandem CD20-CD19-directed non-cryopreserved CAR-T cell therapy. Pediatric patients who are suitable for this study will be treated with MB-CART2019.1. Zamtocabtagene autoleucel (MB-CART2019.1) administration consists of a single infusion with fresh formulation of 2.5 × 10\^6 CAR-transduced autologous T cells/kg bodyweight. IMP is only to be administered after a lymphodepleting chemotherapy with fludarabine and cyclophosphamide. For MB-CART2019.1 production, pediatric patients will undergo a leukapheresis. The enrollment period will last approximately 36 months and the duration of the study for each subject will be 85 weeks (including screening period and a 78 weeks safety follow-up).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
- •Has r/r B-cell neoplasms after one or more prior therapies or primary refractory to first-line therapy.
- •Is a pediatric/adolescent (aged between 6 months and \<18 years).
Exclusion Criteria
- •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.
- •Had allogeneic HSCT.
- •Had autologous HSCT \<120 days prior to written informed consent.
- •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.
- •Subjects with B-cell neoplasms in the context of post-transplant lymphoproliferative disorders-associated lymphomas.
- •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).
- •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.
- •Has history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory diseases.
- •Infection with human immunodeficiency virus (HIV).
- •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.
Arms & Interventions
zamtocabtagene autoleucel (MB-CART2019.1)
Intervention: zamtocabtagene autoleucel (MB-CART2019.1)
Outcomes
Primary Outcomes
Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) [Safety and toxicity of the study product]
Time Frame: From infusion until week 78
The primary safety outcome of this study is to evaluate the incidence, type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) associated with the study product.
BORR, Best Overall Response Rate
Time Frame: From infusion until week 78
The primary efficacy outcome of this study is BORR, defined as the proportion of subjects with at least one partial response (PR) or complete response (CR) from MB-CART2019.1 infusion until progressive disease (PD), start of new anti-lymphoma therapy, lost to follow-up or death, whichever occurs first.