NCT07020260尚未招募1 期
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
Princess Maxima Center for Pediatric Oncology4 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2025年9月1日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Recommended phase 2 dose (RP2D)
研究概览
简要总结
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.
详细描述
In this study patients aged 1-45 years with relapsed or refractory CD19+ hematological malignancies (B-NHL or BCP-ALL) are treated with a single dose of huCAR19 T-cells. After consent and screening, patients will undergo leukapheresis to harvest autologous PBMCs. During the CAR T-cell production, patients receive lymphodepleting chemotherapy after which the huCAR19 T-cells are administered. In phase I the aim is to establish the RP2D, the protocol will then be extended to a phase II.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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 ≥
- •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.
排除标准
- •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.
- •LVSF <28% or LVEF <45% confirmed by echocardiogram or MUGA scan.
- •Concurrent malignancy requiring treatment of having been treated <3 months before screening except for curatively treated basal cell carcinoma of the skin.
- •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.
- •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.
- •Hypersensitivity to the active substance
结局指标
主要结局
Recommended phase 2 dose (RP2D)
时间窗: Within 28 days after huCAR19 infusion.
The endpoint to measure this primary objective is the incidence of dose limiting toxicities (DLTs).
次要结局
- 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))
研究者
研究点 (4)
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