A Study of Natural Killer Cells in Combination With Atezolizumab in People With Acute Myelogenous Leukemia

NCT ID: NCT07011004

Last Updated: 2025-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-30
• Study Completion Date: 2028-05-31

Brief Summary

The researchers are doing this study is to find the highest dose of cytokine-induced memory-like (CIML) natural killer (NK) cells in combination with the drug atezolizumab that causes few or mild side effects in people with relapsed/refractory acute myelogenous leukemia (AML). The researchers will also look at whether the treatment combination works against participants' cancer.

Conditions

Acute Myeloid Leukemia Refractory; Acute Myeloid Leukemia, in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cytokine Induced Memory-Like Natural Killer Cells Combined with Atezolizumb

Pre-conditioning chemotherapy will consist of a standard lymphodepleting regimen including fludarabine 25 mg/m2 IV daily x 5 on days -6 to - 2 and cyclophosphamide 50 mg/kg IV x 2 on days -5 and -4 prior to the infusion of the CIML-NK cells. Standard MSKCC supportive care guidelines for infusion of chemotherapy including cyclophosphamide will be employed. On the day of infusion subjects will receive a single dose of atezolizumab IV over 60 minutes IV. Subjects will receive subcutaneous recombinant human IL-2 (rh-IL2) every other day x 6 doses beginning on day 0 via subcutaneous injection.

Group Type: EXPERIMENTAL

Cytokine Induced Memory-Like Natural Killer Cells

Intervention Type: BIOLOGICAL

Subjects will receive subcutaneous recombinant human IL-2 (rh-IL2) every other day x 6 doses beginning on day 0 via subcutaneous injection.

Atezolizumb

Intervention Type: BIOLOGICAL

Single dose of Atezolizumab IV over 60 minutes IV.

CIML-NK cell therapy

Intervention Type: BIOLOGICAL

CIML-NK cell therapy as an intravenous (IV) infusion

Interventions

Cytokine Induced Memory-Like Natural Killer Cells

Subjects will receive subcutaneous recombinant human IL-2 (rh-IL2) every other day x 6 doses beginning on day 0 via subcutaneous injection.

Intervention Type: BIOLOGICAL

Atezolizumb

Single dose of Atezolizumab IV over 60 minutes IV.

Intervention Type: BIOLOGICAL

CIML-NK cell therapy

CIML-NK cell therapy as an intravenous (IV) infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Subjects must have histologically confirmed acute myeloid leukemia that meets any of the following criteria:

• Refractory to at least two attempts at prior induction therapy. An attempt is defined as either a single cycle of combination chemotherapy such as daunorubicin/anthracycline OR a single monthly cycle of a hypomethylating agent with venetoclax.
• Patients with FLT3-ITD or -TKD mutations must have received at least one commercially available inhibitor of FLT3.
• Patients with NPM1 mutation or rearrangements of MLL must be refractory to revumenib.
• Patients with mutations in IDH1 or IDH2 must be refractory to at least one commercially available inhibitor of IDH1 or IDH2, respectively.
• Relapsed AML when relapse occurred within 6 months of achieving an initial complete remission.
• Patients must have either failed prior FDA approved agents or, in the opinion of the treating physician, have a sufficiently low probability of response to existing FDA approved agents to warrant treatment on an investigational protocol.

• Patients aged 18 through 70 years old are eligible.
• Must have an available, haplotype mismatched related individual that meets criteria for cell donation according to the FACT guidelines.
• Patients must have Karnofsky performance status ≥70%.
• Adequate cardiac function as defined as a systolic LV ejection fraction ≥50% at rest and absence of New York Heart Association stage III or IV congestive heart failure.
• Adequate pulmonary function as defined as a resting SpO2 ≥ 92% on room air at rest.
• Serum bilirubin ≤ 5 mg/dL.
• AST and ALT ≤ 2.5x ULN unless thought to be disease related.
• Estimated or measured creatinine clearance > 50 mL/min.
• Subjects must be free from all systemic immune suppression for at least 4 weeks prior to the start of intended therapy.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Women must refrain from donating eggs during this same period.
• Negative HIV test at screening.
• Negative hepatitis B surface antigen (HBsAg) test at screening OR positive HBsAg is allowed if a negative HBcAb or a negative quantitative hepatitis B virus (HBV) (DNA < 500 IU/mL) assay are documented.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test.
• For patients receiving therapeutic anticoagulation: Stable anticoagulant regimen for 2 weeks prior to enrollment.
• Timing of treatment relative to prior therapies:

• Bridging therapy with hydrea is allowed but is required to be tapered off prior to NK infusion.
• Any experimental biological treatments must be discontinued for at least 5 half-lives prior to initiation of study therapy.
• Patients must be >5 half-lives from receipt of other cytotoxic or targeted therapy.

• Donors must be eligible for apheresis according to standard FACT guidelines.
• Donors must not have an HLA genotype reactive against anti-HLA antibodies in the recipient.

Exclusion Criteria

• Prior allogeneic hematopoietic cell transplantation.
• Subjects with active/uncontrolled CNS leukemia. Subjects with prior CNS disease must have no detectable evidence of CSF disease for at least 4 weeks prior to enrollment.
• Subjects requiring systemic immunosuppression for any indication are excluded.
• Significant cardiovascular disease, as defined by:

• New York Heart Association Class II or greater congestive heart failure.
• Myocardial infarction, cerebrovascular accident, or other arterial vascular disease within 6 months prior to initiation of study treatment
• Unstable arrhythmia
• Unstable angina
• Subjects with isolated extramedullary disease without evidence of bone marrow involvement by immunohistochemistry.
• Female patients who are pregnant or breast-feeding or intend to become pregnant during study treatment or within 5 months after the final dose of atezolizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment with atezolizumab.
• Severe or uncontrolled infection prior to initiation of study treatment.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, excluding prophylactic antimicrobial agents.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12 mg/dL, or corrected calcium greater than ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all following conditions are met:

• Rash must cover < 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Persons who do not meet the age and organ function criteria specified above.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Shaffer, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, United States

Site Status: RECRUITING

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, United States

Site Status: RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States

Site Status: RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)

Commack, New York, United States

Site Status: RECRUITING

Memorial Sloan Kettering West Harrison (Limited Protocol Activities)

Harrison, New York, United States

Site Status: RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activites)

Rockville Centre, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Brian Shaffer, MD

Role: CONTACT

ABMTTrials@mskcc.org

646-608-2091

Mark Geyer, MD

Role: CONTACT

646-608-3745

Facility Contacts

Brian Shaffer, MD

Role: primary

646-608-2091

Brian Shaffer, MD

Role: primary

646-608-2091

Brian Shaffer, MD

Role: primary

646-608-2091

Brian Shaffer, MD

Role: primary

646-608-2091

Brian Shaffer, MD

Role: primary

646-608-2091

Brian Shaffer, MD

Role: primary

ABMTTrials@mskcc.org

646-608-2091

Mark Geyer, MD

Role: backup

646-608-3745

Brian Shaffer, MD

Role: primary

646-608-2091

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

24-356

Identifier Type: -

Identifier Source: org_study_id