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

Prior treatment

• 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.

Other illness

• Hypersensitivity to the active substance
• Active uncontrolled or life-threatening infections
• Renal insufficiency
• Inadequate pulmonary function defined as baseline oxygen saturation <92%, if not caused by underlying disease.
• Inadequate cardiac function

Lab values

• 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 <0.5x10E9/L unless caused by underlying disease
• Platelet count <25x10E9/L unless caused by underlying disease
• Bilirubin and/or transaminases ≤ 2.5 x ULN, unless caused by underlying disease.

Other

• 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.

• 1-45 years of age
• 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.
• Patients with relapsed or refractory CD19+ hematological malignancies (a.o. B-NHL and B-cell precursor)
• Measurable disease (at least one measurable lesion or at least 0.1% of blast in bone marrow)
• Patients must have exhausted or are ineligible for all registered therapeutic options with curative potential.
• Adequate performance score
• 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.