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

• ClinicalTrials.gov Identifier: NCT05077423
• Recruitment Status: Active, not recruiting
• First Posted: October 14, 2021
• Last Update Posted: January 13, 2023
• Sponsor: Y-mAbs Therapeutics
• Collaborator: Children's Oncology Group
• Information provided by (Responsible Party): Y-mAbs Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
AML, Childhood	Drug: CD33*CD3 BsAb	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: open-label, single-arm, dose-escalation consisting of up to 12 cycles
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Dose-escalation Trial of CD33xCD3 Bispecific Antibody in Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia
• Actual Study Start Date: May 25, 2022
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: September 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles; 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 Name: CD33xCD3

Outcome Measures

Primary Outcome Measures :

1. Occurrence of dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
   Occurrence of DLTs during a DLT period .
2. Occurrence of Adverse Events [ Time Frame: 52 weeks ]
   Occurrence of Adverse Events during the trial

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Children's of Alabama/University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, California

Children's Hospital of Orange County

Orange, California, United States, 92868

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94158

United States, District of Columbia

Children's National Hospital

Washington, District of Columbia, United States, 20010

United States, Indiana

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, United States, 46202-5225

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Minnesota

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

United States, Tennessee

St Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

Y-mAbs Therapeutics

Children's Oncology Group

Investigators

• Principal Investigator: Jessica Pollard, MD; Dana-Farber Cancer Institute

More Information

• Responsible Party: Y-mAbs Therapeutics
• ClinicalTrials.gov Identifier: NCT05077423
• Other Study ID Numbers: 801
• First Posted: October 14, 2021
• Last Update Posted: January 13, 2023
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia, Myeloid, Acute; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid