A Phase 1 Trial of CD33xCD3 BsAb in Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia

• 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