The PACMAN-Hu19 trial: a phase I/II study with locally produced CD19-targeted CAR T-cell therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-12-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dutch Cancer Society (KWF)

External identifiers

EU CT number

2023-507597-40-00

ClinicalTrials.gov

NCT07020260

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Therapy

To determine the incidence of DLT within 28 days after CAR T-cel infusion (huCAR19), which will result in the recommended phase 2 dose (RP2D)

Secondary objectives 3

1. To assess preliminary activity at day 28 for the B-ALL cohort, and the overall response rate (CR + PR, according to the Lugano criteria) at day 90 for the B-NHL cohort
2. Duration of response, including the duration of B-cell aplasia
3. Survival estimates including Event Free Survival (EFS, event defined as relapse, refractory disease or death of any cause whichever occurs first), Overall Survival (OS) and Cumulative Incidence of Relapse (CIR)

Conditions and MedDRA coding

B-cell precursor ALL

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1-45 years of age
2. Patients with relapsed or refractory CD19+ hematological malignancies (a.o. B-NHL and B-cell precursor)
3. Measurable disease (at least one measurable lesion or at least 0.1% of blast in bone marrow)
4. Patients must have exhausted or are ineligible for all registered therapeutic options with curative potential.
5. Adequate performance score
6. 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
7. Patients must be willing to abstain from breast feeding through 12 months after administering the last study treatment.
8. Patients must agree to refrain from donating blood or organs following treatment with huCAR19 T-cells.
9. Written informed consent per local law and regulations.
10. Additional inclusion criteria phase I part of the study: The first three patients in the phase 1 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 B-cell Aplasia is reached in ≥60% patients in previous or current dose level.

Exclusion criteria 15

1. Patients with symptomatic CNS involvement will be excluded. After resolution and control of symptoms, patients can be rescreened.
2. Active uncontrolled or life-threatening infections
3. 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.
4. Absolute neutrophil count <0.5x10E9/L unless caused by underlying disease
5. Platelet count <25x10E9/L unless caused by underlying disease
6. Bilirubin and/or transaminases ≤ 2.5 x ULN, unless caused by underlying disease.
7. Renal insufficiency
8. Inadequate pulmonary function defined as baseline oxygen saturation <92%, if not caused by underlying disease.
9. Inadequate cardiac function
10. Concurrent malignancy requiring treatment of having been treated <3 months before screening except for curatively treated basal cell carcinoma of the skin
11. Pregnant women
12. Patients unable to participate in the study according to investigator judgement
13. Patients not willing or unable to adhere to protocol guidelines or follow-up.
14. 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.
15. Hypersensitivity to the active substance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dose at which ≤ 1 patients experience a Dose Limiting Toxicity (DLT) within 28 days after CAR T-cell infusion

Secondary endpoints 9

1. For B-ALL: the MRD-negative CR rate at day 28
2. For B-NHL: the overall response rate (ORR, CR +PR according to Lugano criteria) at day 90
3. Surrogate endpoint for efficacy: B-cell aplasia (<5 B-cells/µl) at day 28 after infusion
4. Number of days until relapse
5. Number of days from CAR T-cell infusion until recovery of B-cells (B-cell recovery is defined as peripheral blood ≥10 CD19+ B-cells/mcL OR ≥1% CD19+ B-cells in the bone marrow. Results must be confirmed on a subsequent test ≥2 weeks apart with timing of B-cell recovery defined as the date of the initial sample
6. Event free survival (EFS) at 6 and 12 months
7. Overall Survival (OS) at 6 and 12 months
8. Cumulative Incidence of Relapse at 6 and 12 months
9. The percentage of products fulfilling the release criteria

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

F.G.J. Calkoen MD PhD

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

F.G.J. Calkoen MD PhD

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Application history

2 submissions — initial application plus substantial / non-substantial modifications