NCT07026942

Phase I/II Clinical Trial of Universal Donor CD33 CAR Natural Killer Cells for AML

A Phase I/II Clinical Trial Evaluating the Safety and Efficacy of Universal Donor CD33 CAR Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 1 Year – 39 Years
• Healthy volunteers: Not accepted

Summary

This phase 1/2 study is testing a new treatment for acute myeloid leukemia (AML) that has come back or has not responded to other treatments. The treatment uses specially modified immune cells (called CD33 CAR-NK cells) from a healthy, unrelated donor to attack the cancer. The first part of the study (Phase I) will focus on finding the safest and most effective dose. The second part (Phase II) will test how well the treatment works at that dose. Patients will undergo screening, chemotherapy (Fludarabine and Cytarabine, in combination with Venetoclax) followed by the infusion of the CD33 CAR NK cells. Some patients may receive 2 doses of CD33 CAR NK cells infused 1 week apart. The investigator will let participants know if they will receive 1 or 2 doses. Patients will be hospitalized for the chemotherapy and CD33 CAR NK cell infusion for close monitoring and will remain in the hospital until blood counts recover. If patients are discharged from the hospital before day 35, they will be followed in clinic weekly for blood work and a physical exam. A bone marrow biopsy will be performed around day 28-35 to see if the patient's leukemia is in remission. Lumbar puncture or imaging may also be done if the study doctor thinks it is necessary. Patients will continue to be followed for research studies and clinical outcomes (leukemia relapse, survival) for 1 year. After 1 year, patients will have completed their study participation, but can be monitored for up to 15 years for potential long term side effects of the cell therapy. Some patients may undergo a bone marrow transplant after the study treatment. Patients who proceed to bone marrow transplant will have one blood sample drawn about a month after the transplant and then will have completed study participation.

Detailed description

This is a phase I/II study designed to determine the safety and estimate the efficacy of CD33 CAR-NK cells combined with FLA-VEN chemotherapy in patients age 1-39.99 with relapsed or refractory acute myeloid leukemia. This study will be performed in two phases: a dose-finding phase and a phase II expansion phase to further study safety and estimate efficacy. To determine the recommended phase II dose investigators will utilize a Bayesian optimal interval (BOIN) dose escalation design. Once a RP2D is established, a phase II expansion cohort of 24 total patients will be enrolled to evaluate efficacy and correlative data while also continually gathering data on safety and toxicity. Manufacturing of the CD33 CAR NK Cells: NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number. Dose Levels * Dose level 1: 1 x 10\^7 CD33 CAR-NK cells/kg * Dose level 2: 3 x 10\^7 CD33 CAR-NK cells/kg * Dose level 3: 1 x 10\^8 CD33 CAR-NK cells/kg * Dose level 4: 2 doses of 1 x 10\^8 CD33 CAR-NK cells/kg Chemotherapy: Days 1-5: Fludarabine 30 mg/m2/d, cytarabine 2g/m2/d Days 1-21: Venetoclax Day 7: CD33 CAR NK infusion Day 14; CD33 CAR NK infusion (for patients on DL4) Patients will be admitted to the hospital for 4-5 weeks during each cycle of treatment for count nadir and recovery.

Conditions

• Relapsed/Refractory AML

Interventions

Type	Name	Description
BIOLOGICAL	Universal donor derived CD33 CAR-NK	Universal donor derived CD38KO CD33 CAR-NK manuctured on-site. The NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number.

Timeline

• Start date: 2026-04-01
• Primary completion: 2032-07-01
• Completion: 2038-07-01
• First posted: 2025-06-18
• Last updated: 2025-11-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study