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Clinical Trial NCT07026942 (CD33 CAR NK) for Relapsed/Refractory AML is not yet recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Phase I/II Clinical Trial of Universal Donor CD33 CAR Natural Killer Cells for AML (CD33 CAR NK) Phase 1, Phase 2 42 Cell Therapy
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...
Show MoreA 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
- CD33 CAR NK
Phase 2
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalCD33 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 C...Show More | 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. |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Phase I : Safety and recommended phase 2 dose | To determine the safety and recommended phase 2 dose of CD33 CAR-NK cells in patients with relapsed/refractory AML investigators will monitor the incidence and severity of adverse events and the rate of dose limiting toxicities. | From the first CD33 CAR NK cell infusion until 28 days after the last CAR NK cell dose. |
Phase II: Efficacy of CD33 CAR NK cells | To estimate the efficacy of CD33 CAR-NK cells delivered at the RP2D with FLA-VEN chemotherapy, the investigators will determine the complete response rate. | Day 35 |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Overall survival, event free survival and duration of remission | To estimate the overall survival, event free survival, and duration of remission in patients who do not proceed to HSCT. | 1 year |
Depth of remission | To determine the percentage of patients who achieve molecular remission and/or MRD negative remission by flow cytometry. | Day 35 |
Events of special interest | To determine the rate of events of special interest including: Cytokine Release Syndrome, Immune Effector Cell Neurotoxicity Syndrome, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome, hepatic VOD, primary graft failure (in patients who undergo HSCT) | 8 weeks post CAR NK, day +30 post HSCT |
Neutrophil recovery | To evaluate the median time to neutrophil and platelet recovery | 1 year |
Patients with relapsed or primary refractory CD33+ AML, including:
- Patients with relapsed AML (patients in second or subsequent relapse, or any relapse after HSCT, are eligible).
- Refractory AML defined as failure to achieve a complete response after 2 cycles of induction or reinduction chemotherapy, including persistent MRD positivity.
- Patients with isolated CNS or extramedullary disease are eligible. Patients with CNS disease are excluded from the phase I dose escalation portion but are eligible for the phase II portion of the study.
1-39.99 years of age (note: the first three subjects treated AND the first subject on each dose level must be ≥ 16 years of age)
Negative serum test to rule out pregnancy within 14 days prior to enrollment in females of childbearing potential
o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
Organ function requirements:
- Renal function: Creatinine ≤ 2 times the institutional upper limit of normal for age OR creatinine clearance > 60 ml/min/1.73m2 (measured by 24 hour- urine specimen or radioisotope GFR)
- Liver function: Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome), AST and ALT ≤ 5 times the upper limit of normal (unless related to leukemic involvement). Upper limit of normal should be determined by the institutional defined normal laboratory range.
- Cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal.
- CNS: Patients with seizure disorder may be eligible if seizures are well controlled
- Pulmonary function: baseline oxygen saturation >92% on room air at rest
Due to the risk of hematopoietic toxicity from CD33 targeting, enrolled subjects must have an allogeneic HCT donor identified and be eligible and willing to undergo a subsequent HSCT in the event of aplasia.
All patients or their legal guardian must be able to understand and willing to sign a written informed consent document.
All patients must consent to enroll in a separate long term follow up study for cell and gene therapy
Prior therapies:
AML directed therapies in the 14 days prior to beginning treatment on this protocol (except for hydroxyurea) Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
Gemtuzumab or other CD33-targeted antibody within 42 days of enrollment
CNS radiation within 28 days of enrollment
DLI or adoptive cell therapy within 30 days of enrollment
Allogeneic SCT within 90 days of enrollment
- Patients with CNS disease are excluded from the phase I portion of the study but are eligible for the phase II expansion phase.
- Patients on immunosuppressive therapy
Patients must be off of systemic immunosuppressive therapy for at least 14 days prior to enrollment with no evidence of recurrent GVHD
Patients on hydrocortisone for treatment of adrenal insufficiency are permitted on study
Patients on corticosteroids ≤ 0.5mg/kg/day (prednisone equivalent) for any other indication are permitted on study
Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the site PI would pose an unacceptable risk to the subject
Patients who are breastfeeding
Patients with prior solid organ transplantation
Performance status: Karnofsky or Lansky Performance Scale (PS) < 50
Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy
o Asymptomatic viremia such as CMV, HPV, BK virus, HCV, etc. is NOT considered as an exclusion criterion
Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
Active acute or chronic GVHD of any grade at the time of enrollment. "Active GVHD" is defined as a patient who requires immunosuppressive therapy for control of their GVHD symptoms.
Nationwide Children's HospitalOhio