The PACMAN-Hu19 Trial: a Study of the Safety and Feasibility of Locally Produced, CD19-targeted and Human CAR T-cell Therapy in Children and Young Adults With Relapsed or Refractory B-cell Malignancies
PACMAN
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
2 other identifiers
interventional
18
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 leukemia
Started Sep 2025
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 26, 2025
CompletedFirst Posted
Study publicly available on registry
June 13, 2025
CompletedStudy Start
First participant enrolled
September 1, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2028
June 13, 2025
June 1, 2025
2 years
February 26, 2025
June 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Recommended phase 2 dose (RP2D)
The endpoint to measure this primary objective is the incidence of dose limiting toxicities (DLTs).
Within 28 days after huCAR19 infusion.
Secondary Outcomes (4)
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: at day 28. For B-NHL: at day 90.
Duration of response, including the duration of B-cell aplasia
from inclusion through study completion
Survival estimates.
Measured at 6 and 12 months.
The feasibility to produce HuCAR19 in the target population.
From day -13 (start of manufacturing) to day 0 (final analysis)
Other Outcomes (7)
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
during treatment
To assess anti-CAR T-immune responses.
From infusion to 12 months after infusion.
Extensive characterization of apheresis product, CAR T-product, and persisting CAR T-cells after infusion
From leukapheresis to 12 months after infusion.
- +4 more other outcomes
Study Arms (1)
huCAR19 T-cells
EXPERIMENTALParticipants will receive one single dose of huCAR19 T-cell infusion on day 0 of the treatment.
Interventions
A single IV infusion of huCAR 19 T-cells on day 0. In phase I 3 dose levels are tested to determine the RP2D.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- +2 more criteria
You may not qualify if:
- 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.
- 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 pulmonary function defined as baseline oxygen saturation \<92%, if not caused by underlying disease.
- Inadequate cardiac function:
- Unstable angina or unstable cardiac arrhythmias.
- NYHA classification \>II.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Princess Maxima Center for Pediatric Oncologylead
- Dutch Cancer Societycollaborator
- Miltenyi Biomedicine GmbHcollaborator
- University Medical Center Utrecht (UMCU)collaborator
Study Sites (2)
University Medical Center Utrecht
Utrecht, Utrecht, 3584 CX, Netherlands
Princess Máxima Center for pediatric oncology
Utrecht, Utrecht, 3584CS, Netherlands
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Friso Calkoen, MD, PhD
Princess Maxima Center for Pediatric Oncology
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 26, 2025
First Posted
June 13, 2025
Study Start
September 1, 2025
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2028
Last Updated
June 13, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share
Only IPD used in the results publication.