A Phase 1, Open-label, Dose-escalation Trial of CD33xCD3 Bispecific Antibody in Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 13
- 主要终点
- Occurrence of dose limiting toxicities (DLTs)
研究概览
简要总结
Pediatric patients (<21 years at study entry) with relapsed or refractory acute myeloid leukemia (AML) will be treated with CD33*CD3 a bispecific antibody to investigate the safety and tolerability of the drug.
详细描述
This is an open label, first in human dose escalation trial in pediatric patients with relapsed or refractory acute myeloid leukemia to assess the safety and tolerability of increasing doses of CD33xCD3 BsAb administered subcutaneously.
A modified Bayesian Optimal Interval Design (mBOIN) design will be applied. The trial will start with accelerated titration using single patient cohorts until one grade ≥2 AE not clearly associated to underlying disease, thereafter the trial will continue with mBOIN titration.
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
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent from legal guardian(s), patient and/or child obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations
- •Age ≥2 years, and ≤21 years, and a minimum body weight of ≥11 kg
- •Histologically confirmed relapsed or refractory AML (except acute promyelocytic leukemia) with no therapeutic options that may provide clinical benefit. Disease burden ≥5.0% in the bone marrow meets definition for enrollment.
- •Karnofsky performance status ≥50 for ≥16 years / Lansky performance status ≥50 for <16 years
- •White blood cells (WBC) ≤25 x 109/L (may receive hydroxyurea to bring WBC count down prior to first dose of CD33xCD3 BsAb and during Cycle 1 or low dose cytarabine up to 48 h prior to first dose of CD33xCD3 BsAb)
- •Central Nervous System (CNS) disease as per Children's Oncology Group
- •Patients must have the status of CNS1 and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
- •Patients with CNS3 or CNS2 status may receive antecedent intrathecal chemotherapy to achieve CNS1 status prior to trial entry
- •Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of disease prior to enrollment
- •Has acceptable liver and kidney laboratory values
- •Patient must have recovered from acute toxic effects of prior anti-cancer therapies prior to first dose of CD33xCD3 BsAb
排除标准
- •History of uncontrolled seizure. If on anti-convulsant and/or seizures are well controlled as per treating physician enrollment is acceptable
- •Acute promyelocytic leukemia with PML-RARA genetic abnormality according to WHO classification or t(15;17)
- •Isolated extramedullary AML
- •Clinically significant graft-versus-host disease (GvHD) secondary to prior allogeneic transplantation. No immunosuppressive therapy for ≥14 days prior to first dose, except for topical corticosteroids for minor rash (<5% of BSA) or adrenal replacement therapy
- •Patient known to have one of the following genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Nijmegen breakage syndrome, Kostmann syndrome, Shwachman Diamond syndrome or any known bone marrow failure syndrome where increased risk for toxicity may be expected as judged by the Investigator
- •Treatment with another investigational agent under the following conditions:
- •Within two weeks (four weeks for biologics) before first administration of CD33xCD3 BsAb; or
- •Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator
研究组 & 干预措施
Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles
Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles
干预措施: CD33*CD3 BsAb (Drug)
结局指标
主要结局
Occurrence of dose limiting toxicities (DLTs)
时间窗: 28 days
Occurrence of DLTs during a DLT period .
Occurrence of Adverse Events
时间窗: 52 weeks
Occurrence of Adverse Events during the trial
次要结局
未报告次要终点