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

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

NCT ID: NCT05672147

Condition: Acute Myeloid Leukemia
Recurrent Adult Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Anti-CD33 CAR T-cells
Description: Given IV
Arm group label: Treatment (anti-CD33 CAR T-cells)

Other name: Anti-CD33 CAR T Cells

Other name: Anti-CD33 CAR-T Cells

Other name: CD33-CAR T Cells

Intervention type: Procedure
Intervention name: Lymphodepletion Therapy
Description: Undergo lymphodepletion
Arm group label: Treatment (anti-CD33 CAR T-cells)

Other name: Lymphodepleting Therapy

Other name: Lymphodepletion

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.

Detailed description: PRIMARY OBJECTIVE: I. Examine the anti-tumor activity and safety of administering patient-specific donor-derived (allogeneic) CD33-CAR T cells following lymphodepletion in research participants with CD33+ recurrent/refractory (r/r) acute myeloid leukemia (AML). SECONDARY OBJECTIVE: I. Assess activity in the form of CAR T cell expansion and persistence, to assess impact on hematopoiesis, 6-month progression free survival (PFS 6mo) rate, duration of response, and 1-year overall survival (OS) rate. EXPLORATORY OBJECTIVES: I. Change from baseline in numbers of CD33+ blood cells, CD33 expression on leukemia cells and hematopoietic cells. II. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred CD33R(CD8h)BBzeta/EGFRt+ T cells. OUTLINE: This is a dose-escalation study. Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells intravenously (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.

Criteria for eligibility:
Criteria:
Inclusion 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 Exclusion Criteria: - 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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: City of Hope Medical Center

Address:
City: Duarte
Zip: 91010
Country: United States

Status: Recruiting

Contact:
Last name: Karamjeet S. Sandhu

Phone: 626-218-2405
Email: ksandhu@coh.org

Investigator:
Last name: Karamjeet S. Sandhu
Email: Principal Investigator

Start date: December 7, 2023

Completion date: September 3, 2026

Lead sponsor:
Agency: City of Hope Medical Center
Agency class: Other

Collaborator:
Agency: National Cancer Institute (NCI)
Agency class: NIH

Source: City of Hope Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05672147