We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT05077423
Recruitment Status : Active, not recruiting
First Posted : October 14, 2021
Last Update Posted : January 13, 2023
Children's Oncology Group
Information provided by (Responsible Party):
Y-mAbs Therapeutics

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.

Layout table for study information
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

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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05077423

Layout table for location information
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
Layout table for investigator information
Principal Investigator: Jessica Pollard, MD Dana-Farber Cancer Institute
Layout table for additonal information
Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT05077423    
Other Study ID Numbers: 801
First Posted: October 14, 2021    Key Record Dates
Last Update Posted: January 13, 2023
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Leukemia, Myeloid