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

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

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.

Study Overview

• Status: Terminated
• Conditions: AML, Childhood
• Intervention / Treatment: Drug: CD33*CD3 BsAb

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama/University of Alabama at Birmingham
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5225
      • Riley Hospital for Children - Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles	Drug: CD33*CD3 BsAb; CD33xCD3 is a bispecific monoclonal antibody, which specifically targets CD33 on the AML blasts and CD3 on the T cells; Other Names: CD33xCD3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of dose limiting toxicities (DLTs)	Occurrence of DLTs during a DLT period .	28 days
Occurrence of Adverse Events	Occurrence of Adverse Events during the trial	52 weeks

Collaborators and Investigators

• Sponsor: Y-mAbs Therapeutics
• Collaborators: Children's Oncology Group
• Investigators: Principal Investigator: Jessica Pollard, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No