PACMAN is a phase I/II single arm, open-label, multi-center study evaluating the safety of human CD19 CAR-T (huCAR19) produced locally using the Miltenyi Prodigy in children, adolescents and young adults with relapsed/refractory CD19+ hematological malignancies for whom no standard of care treatment is available.
1-45 years of age.
B-NHL such as Burkitt lymphoma(BL), de novo or transformed diffuse large B cell lymphoma (DLBCL), lymphoblastic lymphoma (LBL), primary mediastinal B cell lymphoma (PMBCL) or indolent lymphoma types with no access to commercially available CAR T-cell therapy or for whom the current production time for commercially available CAR T-cell therapy is not acceptable based on medical need.
B-cell precursor ALL failing commercially available CAR T-cell therapy, or for BCP-ALL indications with no access to commercially available CAR T-cell therapy, or for whom the current production time for commercially available CAR T-cell therapy is not acceptable based on urgent medical need (the latter needs to be confirmed by the sponsor).
For B-NHL at least one measurable lesion according to the Lugano classification.
Patients with symptomatic CNS involvement will be excluded. After resolution and control of symptoms, patients can be rescreened.
Active uncontrolled or life-threatening infections.
Infection with HTLV-1, HTLV-2, HIV-1, HIV-2, hepatitis B (HbsAg positive) or hepatitis C (anti-HCV positive). Chronic controlled hepatitis B or C infection with undetectable viral load or controlled HIV infection with viral load <50 IU/ml and CD4+ T-cell count >200/ml may be considered when antiviral prophylaxis or therapy can be administered.
Absolute neutrophil count <0.5x109/L unless caused by underlying disease.
Sequential
CAR T-cell and Cellular Therapies
Other interventionA single IV infusion of huCAR 19 T-cells on day 0. In phase I 3 dose levels are tested to determine the RP2D.
Recommended phase 2 dose (RP2D)
The endpoint to measure this primary objective is the incidence of dose limiting toxicities (DLTs).
To assess preliminary activity at day 28 for the BCP-ALL cohort and the overall response rate for the B-NHL cohort
For BCP-ALL: the MRD-negative CR rate. For B-NHL: the overall response rate (ORR, CR +PR according to Lugano criteria).
Duration of response, including the duration of B-cell aplasia
Number of days until relapse. Number of days until loss of B-cell aplasia defined by ≥ 5 B-cells/µl.
Survival estimates.
Event free survival (EFS); Overall survival (OS); Cumulative Incidence of Relapse (CIR).
The feasibility to produce HuCAR19 in the target population.
Percentage of products fulfilling the release criteria.
To assess protein levels during treatment including cytokines reported to correlate with specific adverse events of interest of CAR T-therapy, namely CRS and ICANS
Protein expression.
To assess anti-CAR T-immune responses.
Antibody formation and changes in immune cell subsets.
Extensive characterization of apheresis product, CAR T-product, and persisting CAR T-cells after infusion
Immunophenotype of apheresis product, CAR T-product and persisting CAR T-cells after infusion. CAR T-cell expansion (peak expansion, AUC of first 28 days).
Measure levels of fludarabine during the lymphodepleting regimen
Measure levels of fludarabine in peripheral blood.
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Princess Maxima Center for Pediatric Oncology
Lead sponsor
Dutch Cancer Society
Collaborator
Miltenyi Biomedicine GmbH
Collaborator
University Medical Center Utrecht (UMCU)
Collaborator
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