CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia

NCT05672147 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21665NCI-2022-10310P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient or donor's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's or donor's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.

Conditions

Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Participants who achieve measurable residual disease (MRD)

  Defined as complete response (CR) or MRD- complete response with incomplete hematopoietic recovery. Rates and associated 90% Clopper and Pearson binomial confidence limits.

  Up to 15 years post study treatment

• Incidence of dose-limiting toxicities and full toxicity profile

  Rates and associated 90% toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0, and modified Cytokine Release Syndrome grading as applicable. Clopper and Pearson binomial confidence limits.

  Up to 1 year following the last CAR T cell infusion

Secondary Outcomes (5)

• Expansion and persistence of the CAR T cell product

  Up to 15 years post-CAR T cell infusion

• Percent and counts from peripheral blood cell subsets in hematopoietic stem/progenitor cell compartments

  Up to 15 years post-CAR T cell infusion

• Duration of response

  From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years post CAR T cell infusion

• Progression-free survival

  From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years post CAR T cell infusion

• Overall survival

  from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years post CAR T cell infusion

Study Arms (1)

Treatment (anti-CD33 CAR T-cells)

EXPERIMENTAL

Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells IV on day 0. Patients with persistent CD33+ AML who are \> 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.

Biological: Anti-CD33 CAR T-cells; Procedure: Lymphodepletion Therapy

Interventions

Anti-CD33 CAR T-cells BIOLOGICAL

Given IV

Also known as: Anti-CD33 CAR T Cells, Anti-CD33 CAR-T Cells, CD33-CAR T Cells

Treatment (anti-CD33 CAR T-cells)

Lymphodepletion Therapy PROCEDURE

Undergo lymphodepletion

Also known as: Lymphodepleting Therapy, Lymphodepletion

Treatment (anti-CD33 CAR T-cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening, while the request for a translated full consent is processed
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with Study principal investigator (PI) approval
• Age: \>= 18 years
• Karnofsky Performance Scale (KPS) \>= 70
• Life expectancy \>= 16 weeks at the time of enrollment
• Prior allogeneic transplant allowed if \> 6 months prior to study enrollment
• Participant must have a confirmed diagnosis of active CD33+ AML de novo, or secondary OR participants who are at a high risk for disease recurrence
• Relapsed AML is defined as patients that had a first complete response (CR) before developing recurrent disease (increased bone marrow blasts)
• Refractory AML is defined as patients that have not achieved a first CR after induction chemotherapy. For patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy
• Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML
• CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry. Cytogenetics, flow cytometry, and molecular studies (such as FLT-3 status) will be obtained as per standard practice
• Research participants who are at a high risk of disease recurrence, they must have historical bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML

You may not qualify if:

• Prior allogeneic transplant if \< 6 months prior to enrollment
• Participants with active autoimmune disease, including graft versus host disease (GvHD), requiring systemic immune suppressive should be stopped 28-days prior to enrollment
• Participants may not be receiving any other investigational agents and are not dependent on concurrent biological therapy, chemotherapy, or radiation therapy
• With exception to Hydrea which must be stopped prior to initiation of lymphodepletion
• Research participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. However, participants on antifungal prophylaxis are eligible
• Not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
• Subjects with \>= Grade 2 myelofibrosis on bone marrow biopsy
• Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening if the patient is undergoing leukapheresis. Patients with controlled atrial arrythmia is allowed
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to screening
• Subjects with presence of other active malignancy, however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection based on testing performed within 4 weeks of enrollment
• Active viral hepatitis

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

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

• Karamjeet S Sandhu

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): September 3, 2028
• Study Completion (Estimated): September 3, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)