NK Cell Infusion for Patients With Acute Myeloid Leukemia

Clinical Study of Natural Killer Cell Infusion in Patients With Acute Myeloid Leukemia

Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms. In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology, NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. In this clinical trial the investigators want to demonstrate the safety and efficacy chemotherapy combined with donor-derived in vitro activated NK cells infusion for high risk AML patients.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: chemotherapy combined with NK cells infusion

Detailed Description

Despite improvements in new drugs and allogeneic stem cell transplantation (allo-SCT), relapse remains a problem for patients with acute myeloid leukemia (AML). Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms.

In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology (GMP technology), NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. Preclinical studies have confirmed that adoptive infusion expanded and activated NK cells can specifically recognize and kill tumor cells in mice without causing GVHD, which is a safe and effective treatment.

Therefore, in this clinical trial the investigators want to enroll patients with acute AML (excluding APL) who are continued to be unresolved, or relapsed after remission, or continued to be MRD-positive after induction and consolidation according to NCCN standard chemotherapy regimen. Chemotherapy was combined with donor-derived in vitro activated NK cells infusion to evaluate the safety and effectiveness effect of NK cells and to explore the dynamics of NK in vivo after adoptive infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Institute of Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. AML patients receiving standard NCCN induction and consolidation chemotherapy;
2. Age> = 18 years old;
3. Relapsed and refractory AML: continued non-remission after induction and consolidation chemotherapy with NCCN standard protocol, or relapse after remission, or continued MRD positive;
4. MDS-RAEB, MDS-AML, MPD-AML;
5. ECOG≤3;

6. No serious organ dysfunction within 2 weeks before treatment:

   1. Heart: no arrhythmia and LVEF≥50% and no pericardial effusion;
   2. Liver: liver function <2 times the upper limit of ALT and <1.5 times the upper limit of total bilirubin, no active hepatitis;
   3. Kidney: serum creatinine <1.5 mg / dl; or if serum creatinine exceeds the upper limit, serum creatinine clearance should be CrCl> 50 ml / min;
   4. indoor fingertip blood oxygen saturation ≧ 92%;
7. Expected survival time ≥ 3 months;
8. The interval between re-induction therapy and NK cell therapy is at least 2 weeks, and the toxic and side effects of all induction remission treatments have disappeared; if the patient is receiving non-invasive chemotherapy, such as hydroxyurea, low-dose cytarabine, before receiving this program Should be discontinued before;
9. All patients and donors are willing to join this clinical trial and sign informed consent.

Exclusion Criteria:

1. Combined with a history of other malignant tumors <5 years (except cured skin basal cell carcinoma, cured cervical carcinoma in situ and gastrointestinal tumors confirmed to be cured by endoscopic mucosal resection);
2. Have received bone marrow or organ transplant;
3. Those who are allergic to the biological agents used in this treatment;
4. active infection;
5. Those who received other cell treatments such as DLI, CMV-CTL, EBV-CTL;
6. HBV carriers;
7. Patients with extramedullary recurrence;
8. Chest radiographic examination to determine patients with pulmonary inflammation;
9. Researchers do not consider it appropriate to participate in this trial.

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: AML patients with NK cells infusion; The relapsed/refractory AML patient received Flu+CTX (Flu 25mg/m2 (-6d to -2d)，CTX 1.0g/m2 (-6d to -5d) and haploidentical NK cells infusion postchemotherapy for at least 48 hours. NK cell dose was over 1+E07/ kg with 3 consecutive infusions. NK cells infusion interval was 1 day.	Drug: chemotherapy combined with NK cells infusion; chemotherapy combined with NK cells infusion; Other Names: cyclophosphamide (Cy, 1000 mg/m2/day, day -6 to -5), and fludarabine (Flu, 25 mg/m2/day, day -6 to -2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Closely monitor the patient's temperature, rash, BP, and other adverse reactions during the 48 hours after the infusion, and pay attention to acute and chronic GVHD; follow up once every 1-2 weeks within 6 months after the infusion, and review the blood count and biochemistry. Increase or decrease the relevant inspections and inspection frequencies as appropriate according to the condition;	Two months after NK treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants acheived CR post NK treatment	To evaluate the CR rate 1 month after NK treatment	One month after NK treatment
Monitor the metabolism, migration and reconstruction of NK cells in vivo post NK treatment	The number of NK cells were evaluated before and after the completion of the infusion.	One month after NK treatment
Assess the cell count recovery time of peripheral blood in chemotherapy combined with NK infusion	The blood count were evaluated closely before and after the completion of the infusion.	Two months after NK treatment
Number of participants relapsed post NK treatment	To evaluate the bone marrow status every months after NK treatment	Every months after NK treatment within 1 year

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: The University of Science and Technology of China
• Investigators: Principal Investigator: Xiao-Jun Huang, M.D., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 30, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: 2019PHD005-01

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
• product manufactured in and exported from the U.S.: No