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

NCT05077423 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 801
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 13

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.

Conditions

AML, Childhood

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles

EXPERIMENTAL

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

Drug: CD33*CD3 BsAb

Interventions

CD33*CD3 BsAb DRUG

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

Also known as: CD33xCD3

Subcutaneous administration of CD33*CD3 BsAb up to 12 cycles

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead
• Children's Oncology Group: collaborator

Study Sites (13)

Children's of Alabama/University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Riley Hospital for Children - Indiana University

Indianapolis, Indiana, 46202-5225, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jessica Pollard, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label, single-arm, dose-escalation consisting of up to 12 cycles

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: October 14, 2021
• Study Start: May 25, 2022
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 30, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)