Clinical trial NCT05333705: Donor Immune Cell Therapy for Acute Myeloid Leukemia
Official title: Trial of Donor Immune Cell Therapy for Acute Myeloid Leukemia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: natural killler cell
Acute Myeloid Leukemia
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2022-04-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Study Arms: Experimental arm: Cytokine Arm Infusions of Natural Killer (NK) cells
Primary purpose: TREATMENT

Brief summary: This study aims to introduce a new technology of donor NK cell infusion. NK cells defend against viruses and cancer cells in vivo whereas this effect declines in patiens with tumors. In this study, NK cells will be separated from donated peripheral blood or umbilical cord blood. Eligible NK cells will be infused to patients with Acute myeloid leukemia (AML). This new therapy will probably induce their sustained remission and reduce recurrences.

Detailed description: Primary end point:

To determine the rate of overall survival at 2 years of Interventional cohort

Secondary end point:

To determine the cumulative incidence of relapse at 2 years. To determine the rate of disease-free survival at 2 years. Describe the safety and toxicity of donor NK cell infusion.

Study Design:

This study is a phase I clinical trial. 15 eligible AML patients will be enrolled sequentially to receive detached NK cells product during induction or consolidation therapy. Refractory or relapsed patients and patients who achieved complete remission (CR) after induction therapy are included. They will receive anthracycline-based chemotherapy according to NCCN guidelines. At the same time, Cultured NK cells will be infused into patients after chemotherapy. Anti-allergic therapy and prophylaxis of graft versus host disease (GVHD) will be given before infusion. Treatment effect will be measured and adverse effect will be treated and documented after intervention.

Eligibility criteria: Inclusion Criteria:

* Patients must have been diagnosed as acute myeloid leukemia in accordance with "Chinese Diagnosis and Treatment Guidelines of AML". Those who achieved CR after chemotherapy are mainly included. Refractory/relapsed AML can also be enrolled.
* Patients with normal heart function (ejection fraction ≥ 50%), normal liver function(ALT and AST ≤ 2.5 times the upper limit of normal value, bilirubin ≤ 2 times the upper limit of normal value) and normal renal function with blood creatinine ≤ 3.0 mg/dL (≤ 260 µmol /L) can be enrolled.
* Patients will be required to sign an informed consent.

Exclusion Criteria:

* Patients with severe infection or other malignant tumors.
* Women during pregnancy or lactation.
* Other patients deemed unsuitable by the investigator.

Primary outcomes:
measure: hematological response rate
timeFrame: up to 2 years, from treatment begining to death
measure: Overall survival
timeFrame: Up to 2 years after beginning treatment
Secondary outcomes:
measure: Cumulative incidence of relapse
timeFrame: Up to 2 years after beginning treatment
measure: Disease free survival (DFS)
timeFrame: Up to 2 years after beginning treatment
measure: Incidence of adverse effects
timeFrame: Up to 2 years after beginning treatment
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: huaiyu Wang, doctor
role: STUDY_CHAIR
References:
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citation: Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005 Apr 15;105(8):3051-7. doi: 10.1182/blood-2004-07-2974. Epub 2005 Jan 4.
citation: Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014 Jun 19;123(25):3855-63. doi: 10.1182/blood-2013-10-532531. Epub 2014 Apr 9.
citation: Curti A, Ruggeri L, Parisi S, Bontadini A, Dan E, Motta MR, Rizzi S, Trabanelli S, Ocadlikova D, Lecciso M, Giudice V, Fruet F, Urbani E, Papayannidis C, Martinelli G, Bandini G, Bonifazi F, Lewis RE, Cavo M, Velardi A, Lemoli RM. Larger Size of Donor Alloreactive NK Cell Repertoire Correlates with Better Response to NK Cell Immunotherapy in Elderly Acute Myeloid Leukemia Patients. Clin Cancer Res. 2016 Apr 15;22(8):1914-21. doi: 10.1158/1078-0432.CCR-15-1604. Epub 2016 Jan 19.