Donor Immune Cell Therapy for Acute Myeloid Leukemia

Trial of Donor Immune Cell Therapy for Acute Myeloid Leukemia.

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: infusion of natural killer cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: huaiyu Wang, doctor; Phone Number: 0086-18991232410; Email: whymed@126.com
• Study Contact Backup: Name: sha Gong, doctor; Phone Number: 0086-18710720955; Email: 314621649@qq.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710016
      • Recruiting
      • First Affiliated Hospital of Xian Jiaotong University
      • Contact: Huaiyu Wang, Doctor; Phone Number: 0086-15809207527; Email: whymed@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: immune cell arm; Umbilical cord blood or donated peripheral blood of healthy donors were collected and NK cells were cultured. NK cell production will be infused after chemotherapy.	Biological: infusion of natural killer cells; Umbilical cord blood or donated peripheral blood of healthy donors were collected and NK cells were sorted and cultured. NK cell production will be infused after chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hematological response rate	Hematological Complete Remission (HCR): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0x10^9/L; platelet count >100x10^9/L.	up to 2 years, from treatment begining to death
Overall survival	Overall survival (OS) is measured from the date of first infusion of NK cells to the date of death from any cause; patients not known to have died at last follow up are censored on the date they were last known to be alive.	Up to 2 years after beginning treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of relapse	Relapse was defined as the recurrence of above 5%bone marrow blasts and the reappearance of blasts in the blood or the development of extramedullary disease infiltrates at any site.	Up to 2 years after beginning treatment
Disease free survival (DFS)	Disease free survival (DFS) is defined as the time from the date of first infusion of NK cells to the date of relapse or death as a result of any cause.	Up to 2 years after beginning treatment
Incidence of adverse effects	Toxic effects were graded according to the National Cancer Institute's Common Toxicity Criteria.	Up to 2 years after beginning treatment

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Study Chair: huaiyu Wang, doctor, First Affiliated Hospital Xi'an Jiaotong University

Publications and helpful links

General Publications

• Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, Urbani E, Negrin RS, Martelli MF, Velardi A. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood. 1999 Jul 1;94(1):333-9.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 17, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 17, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; natural killler cell
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: XJYFY-2020N8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No