RECRUITING

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

Description

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.

Study Overview

Study Details

Study overview

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.

Phase I Study of Cellular Immunotherapy Using T Cells Lentivirally Transduced to Express a Cd33-Specific Chimeric Antigen Receptor for Patients With Cd33+ Relapsed/Refractory Acute Myeloid Leukemia

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

Condition
Acute Myeloid Leukemia
Intervention / Treatment

-

Contacts and Locations

Duarte

City of Hope Medical Center, Duarte, California, United States, 91010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * 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
  • * No known contraindications to lymphodepleting agents, steroids, tocilizumab and/or cetuximab, or the investigational agent
  • * Total serum bilirubin =\< 2.0 mg/dL
  • * Participants with Gilbert syndrome may be included if their total bilirubin is =\< 3.0
  • * Aspartate aminotransferase (AST) =\< 3 x the upper limit of normal (ULN)
  • * Alanine aminotransferase (ALT) =\< 3 x ULN
  • * Estimated creatinine clearance of \>= 60 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis
  • * Left ventricular ejection fraction \>= 50% within 8 weeks before enrollment
  • * Oxygen (O2) saturation \> 92% not requiring oxygen supplementation
  • * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  • * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  • * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  • * Research participants must have a potential donor or stem cell source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical)
  • * DONOR: The identified donor must be the original donor whose stem cells were used for the research participant's allogeneic hematopoietic stem cell transplantation (alloSCT)
  • * DONOR: The donor must be HIV negative
  • * DONOR: KPS \>= 70
  • * DONOR: Documented body weight
  • * Prior allogeneic transplant if \< 6 months prior to enrollment
  • * Concurrent use of systemic steroids or chronic use of immunosuppressant medications should be stopped 28-days prior to enrollment. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =\< 7.5 mg/day, or equivalent doses of other corticosteroids) is allowed
  • * 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
  • * Females only: Pregnant or breastfeeding
  • * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
  • * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

City of Hope Medical Center,

Karamjeet S Sandhu, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

2026-09-03