Locally made CAR T-cell therapy for young people with relapsed B-cell cancers

Trial details

Who runs it

Princess Maxima Center for Pediatric Oncology

Trial code

NCT07020260EU 2023-507597-40-00

Record updated

13 June 2025

Original description

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.Read full original descriptionShow less

The PACMAN-hu19 Trial: a Phase I/II Study to Investigate the Safety and Feasibility of Point-of-care Human CD19 Targeting CAR T-cells in Pediatric and Young Adult Patients With Relapsed or Refractory B-cell Malignancies

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.

Inclusion: 1-45 years of age; Patients with relapsed or refractory CD19+ hematological malignancies including, but not limited to:; 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; OR; 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); Measurable disease:; For B-NHL at least one measurable lesion according to the Lugano classification; For BCP-ALL at least 0.1% (=10-3) of blasts should be present in the bone marrow measured by molecular MRD, morphology or flow cytometry at screening; Patients must have exhausted or are ineligible for all registered therapeutic options with curative potential; Adequate performance score:; Children <16 years: Lansky performance status ≥ 60 ; Children age ≥16 years and <18 years Karnofsky performance status ≥ 60; Adults ≥18 years ECOG performance status 0, 1 or 2 (ECOG performance status 3 is allowed only when due to underlying disease); Patients from childbearing potential must be willing and able to use highly effective methods of birth control from first chemotherapy infusion through 12 months after administering the last study treatment; Patients must be willing to abstain from breast feeding through 12 months after administering the last study treatment; Patients must agree to refrain from donating blood or organs following treatment with huCAR19 T-cells; Written informed consent per local law and regulations; Additional inclusion criteria phase I part of the study:; The first three patients in the phase I part of the study must be aged 12-45 years, thereafter patients of any age between 1-45 years can be recruited once surrogate endpoint of BCA is reached in ≥60% patients in previous or current dose level and ≤1 DLT occurred at the previous dose level.

Exclusion: Concurrent malignancy requiring treatment of having been treated <3 months before screening except for curatively treated basal cell carcinoma of the skin; Treatment with allogeneic stem cell transplantation <12 weeks from screening or DLI <4 weeks from screening or active GVHD requiring systemic treatment. Cutaneous GVHD requiring only topical steroids is allowed; Active uncontrolled or life-threatening infections; Inadequate pulmonary function defined as baseline oxygen saturation <92%, if not caused by underlying disease; Hypersensitivity to the active substance; 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; Platelet count <25x109/L unless caused by underlying disease; Bilirubin and/or transaminases ≤ 2.5 x ULN, unless caused by underlying disease; Renal insufficiency, defined as:; For adults (≥18 years) glomerular filtration rate (GFR) < 45 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation:; predicted GFR (ml/min/1.73 m2) = 186 x (serum creatinine in umol/L / 88.7) - 1.154 x (age in years) - 0.203 x (0.742 if patient is female) x (1.212 if patient is black); For children (<18 years) a serum creatinine based on gender/age as follows (in µmol/l):; Age Male Female 0 to < 2 years 53 70 2 to < 6 years 70 70 6 to < 10 years 88 88 10 to < 13 years 106 106 13 to < 16 years 132 123 16 to < 19 years 150 123; Inadequate cardiac function:; Unstable angina or unstable cardiac arrhythmias; NYHA classification >II; LVSF <28% or LVEF <45% confirmed by echocardiogram or MUGA scan; Patients with symptomatic CNS involvement will be excluded. After resolution and control of symptoms, patients can be rescreened; Pregnant women; Patients unable to participate in the study according to investigator judgement; Patients not willing or unable to adhere to protocol guidelines or follow-up.

ClinicalTrials.gov NCT07020260 · EU CTIS 2023-507597-40-00