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

NCT ID: NCT05077423

Last Updated: 2023-05-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-25
• Study Completion Date: 2022-12-01

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.

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.

Conditions

AML, Childhood

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles

Subcutaneous administration of CD33\*CD3 BsAb up to 12 cycles

Group Type: EXPERIMENTAL

CD33*CD3 BsAb

Intervention Type: DRUG

CD33xCD3 is a bispecific monoclonal antibody, which specifically targets CD33 on the AML blasts and CD3 on the T cells

Interventions

CD33*CD3 BsAb

CD33xCD3 is a bispecific monoclonal antibody, which specifically targets CD33 on the AML blasts and CD3 on the T cells

Intervention Type: DRUG

Other Intervention Names

CD33xCD3

Eligibility 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Oncology Group

NETWORK

Sponsor Role: collaborator

Y-mAbs Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Pollard, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Children's of Alabama/University of Alabama at Birmingham

Birmingham, Alabama, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Other Identifiers

801

Identifier Type: -

Identifier Source: org_study_id