Study of Anti-CD33 Chimeric Antigen Receptor-Expressing T Cells (CD33CART) in Children and Young Adults With Relapsed/Refractory Acute Myeloid Leukemia

NCT03971799 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17-CD33CART
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 6

Brief Summary

This phase 1/2 trial aims to determine the safety and feasibility of antiCD33 chimeric antigen receptor (CAR) expressing T cells (CD33CART) in children and adolescents/young adults (AYAs) with relapsed/refractory acute myeloid leukemia (AML). The trial will be done in two phases: Phase 1 will determine the maximum tolerated dose of CD33CART cells using a 3+3 trial design, with dose-escalation for autologous products separated from dose-escalation for an allogeneic arm. Phase 2 is an expansion phase designed to evaluate the rate of response to CD33CART.

Conditions

Acute Myelogenous Leukemia

Keywords

CD33CART cells; Children/young adults

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose - Autologous Arm

  To determine the maximum tolerated dose of lentivirally-transduced autologous CD33-redirected CAR-T cells (CD33CART) in children and young adults with relapsed/refractory AML

  Day 28 post CD33CART infusion

• Maximum tolerated dose - Allogeneic Arm

  To determine the maximum tolerated dose of lentivirally-transduced allogeneic CD33-redirected CAR-T cells (ALLO-CD33CART) in children and young adults with post-HSCT relapsed/refractory AML

  Day 28 post CD33CART infusion

• Morphologic remission

  To determine the percentage of recipients treated with CD33CART who achieve morphologic remission (\<5% blasts in marrow) at Day 28 post-CD33CART cell infusion

  Day 28 post CD33CART infusion

Secondary Outcomes (11)

• Feasibility of CD33CART manufacture

  2 weeks post start of CD33CART manufacture

• Feasibility of CD33CART infusion

  6 weeks post apheresis

• Molecular Cytokine release syndrome (CRS), sinusoidal occlusion syndrome (SOS), or other CD33CART related toxicities

  8 weeks post CD33CART infusion

• Overall survival, event-free survival and treatment-related mortality

  28 days post CD33CART infusion

• Morphologic remission

  28 days post CD33CART infusion

Study Arms (2)

CD33CART autologous

EXPERIMENTAL

Patients who receive an autologous CD33CART cell infusion

Biological: CD33CART autologous

CD33 CART allogeneic

EXPERIMENTAL

Patients who receive an allogeneic CD33CART cell infusion

Biological: CD33CART allogeneic

Interventions

CD33CART autologous BIOLOGICAL

The treatment regimen will consist of lymphodepleting (LD) chemotherapy followed by autologous CD33CART infusion: LD option #1 (IV fludarabine 25 mg/m2/dose administered Days -4 to -2 and IV cyclophosphamide 900 mg/m2/dose on Day -2) or LD option #2 (IV fludarabine 30 mg/m2 on days -5, -4, -3, and -2; and IV cyclophosphamide 500 mg/m2 on days -3 and -2). Subjects will then proceed to allogeneic HCT or alternative therapy as clinically applicable.

CD33CART autologous

CD33CART allogeneic BIOLOGICAL

The treatment regimen will consist of lymphodepleting (LD) chemotherapy followed by allogeneic CD33CART infusion: LD option #1 (IV fludarabine 25 mg/m2/dose administered Days -4 to -2 and IV cyclophosphamide 900 mg/m2/dose on Day -2) or LD option #2 (IV fludarabine 30 mg/m2 on days -5, -4, -3, and -2; and IV cyclophosphamide 500 mg/m2 on days -3 and -2). Subjects will then proceed to allogeneic HCT or alternative therapy as clinically applicable.

CD33 CART allogeneic

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recipients must have CD33+ AML in second or greater relapse, post-transplant relapse, or have demonstrated chemotherapy-refractory disease (definitions in criteria 2c) to be eligible to participate in this trial.
• Disease status at the time of enrollment:
• Recipients in second or greater relapse will be eligible with relapse defined as \>5% blasts (bone marrow) after second documented complete remission
• Any degree of detectable disease post-transplant relapse will be eligible (with flow cytometric confirmation of CD33+ myeloid leukemia of at least 0.1%)
• Refractory disease is defined as persistent bone marrow involvement with \>5% blasts after two courses of induction chemotherapy for patients at initial presentation or \>5% bone marrow blasts after one course of re-induction chemotherapy for patients in relapse;
• CD33 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry;
• Age: Greater than or equal to 1 year of age and less than or equal to 35 years of age at time of enrollment.
• All recipients must have an allogeneic HCT donor identified with a plan to proceed to HCT conditioning within 6-8 weeks of CD33CART cell infusion;
• Patients with two prior allogenic donor stem cell transplants must be medically fit for a third allogenic donor stem cell transplant
• Performance status: \> 50% (for recipients \> 16 years of age use Karnofsky ≥ 50%; recipients \< 16 years of age: Lansky scale ≥ 50%) (see Appendix II). Recipients who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for the purpose of calculating the performance score;
• Adequate organ function as defined by:
• Cardiac function: left ventricular ejection fraction (LVEF) ≥ 45% or fractional shortening ≥28%
• Pulmonary function: baseline oxygen saturation \> 92% on room air at rest
• Hepatic function:
• Total bilirubin \< grade 2 bilirubin CTCAE version 5 (\<3 x ULN) (except in case of recipients with documented Gilbert's disease \> 3 x ULN)

You may not qualify if:

• Recipients meeting any of the following criteria are not eligible for participation in the study:
• Recipients with radiologically-detected CNS chloromas or CNS 3 disease (presence of ≥ 5/μL white blood cells (WBCs) in cerebral spinal fluid (CSF) and cytospin positive for blasts \[in the absence of a traumatic lumbar puncture\] and/or clinical signs of CNS leukemia such as a cranial nerve palsy from active disease). Recipients with adequately treated CNS leukemia are eligible;
• Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
• Pregnancy (negative serum or urine pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen);
• Breast feeding;
• Sexually active female recipients of childbearing potential and male recipients who are of childbearing potential and are unwilling to practice birth control at time of enrollment and for four months after receiving the lymphodepletion preparative regimen;
• Active or uncontrolled viral, bacterial or fungal infection. May be receiving ongoing therapy for controlled infection
• Recent prior therapy:
• At treatment enrollment:
• Patients may be on lower-intensity chemotherapy (e.g., TKIs, venetoclax, hydroxyurea, azacytidine, decitabine or similar agents) at the time of enrollment to prevent disease progression. There is no timing restriction of intrathecal chemotherapy for enrollment.
• Prior to apheresis: The following wash-out periods apply prior to apheresis
• Systemic chemotherapy ≤ 14 days with the exception of:
• Hydroxyurea: 1 day
• Azacytidine/decitabine and/or venetoclax: 7 days
• Intrathecal chemotherapy \> 3 days

Sponsors & Collaborators

• Center for International Blood and Marrow Transplant Research: lead
• National Marrow Donor Program: collaborator
• St. Baldrick's Foundation: collaborator

Study Sites (6)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

National Cancer Institute - NIH

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital/Fred Hutchinson Cancer Research Center

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Qin H, Yang L, Chukinas JA, Shah N, Tarun S, Pouzolles M, Chien CD, Niswander LM, Welch AR, Taylor N, Tasian SK, Fry TJ. Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design. J Immunother Cancer. 2021 Sep;9(9):e003149. doi: 10.1136/jitc-2021-003149.

  PMID: 34531250 DERIVED

Related Links

• Anti-CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
• CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

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

• Nirali Shah, MD, MHSc

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

• Richard Aplenc, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: A 3+3 dose escalation design will be used to determine maximum tolerated dose for both autologous and allogeneic recipients in Phase 1 and Simon's two-stage design will be used to evaluate the efficacy of CD33CART in Phase 2.

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: June 3, 2019
• Study Start: January 8, 2020
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2039
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)