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

Conditions

• Relapsed/Refractory AML

Eligibility Criteria

Sex

ALL

Age

1 Year - 39 Years

Healthy Volunteers

Not accepted

Interventions

• Universal donor derived CD33 CAR-NK — BIOLOGICAL
  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.

Study Details

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.

Key Dates

Start date

Apr 1, 2026

Status verified

Nov 2025

Primary completion

Jul 1, 2032

Completion

Jul 1, 2038

Study Design

Enrollment

42 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: CD33 CAR NK Cells
  Patients will undergo 5 days of lymphodepleting chemotherapy (Fludarabine and Cytarabine) along with oral Venetoclax given from days 1-21 of the cycle. CD33 CAR NK cells will be infused on day 7 (and day 14 for dose level 4). 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

Primary Outcome Measure

Phase I : Safety and recommended phase 2 dose [ Time Frame: From the first CD33 CAR NK cell infusion until 28 days after the last CAR NK cell dose. ]

Central Contacts

• Clelie Peck
  614-722-5634
  [email protected]

Locations (1)

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