A Phase 1, Open-label, Dose-escalation Trial of CD33xCD3 Bispecific Antibody in Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia

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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.

2022-05-25

2022-12-01

2022-12-01

Terminated

Early phase I

3

Inclusion Criteria: * 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 Exclusion Criteria: * 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'open-label, single-arm, dose-escalation consisting of up to 12 cycles', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 3, 'type': 'ACTUAL'}}

2023-05-30