NK Cell Infusion for Patients With Acute Myeloid Leukemia

NCT ID: NCT04221971

Last Updated: 2020-10-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-31
• Study Completion Date: 2022-04-30

Brief Summary

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.

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.

Conditions

Acute Myeloid Leukemia

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

chemotherapy combined with NK cells infusion

Intervention Type: DRUG

chemotherapy combined with NK cells infusion

Interventions

chemotherapy combined with NK cells infusion

chemotherapy combined with NK cells infusion

Intervention Type: DRUG

Other Intervention Names

cyclophosphamide (Cy, 1000 mg/m2/day, day -6 to -5), and fludarabine (Flu, 25 mg/m2/day, day -6 to -2)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Science and Technology of China

OTHER

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Huang,MD

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Jun Huang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

Peking University Institute of Hematology

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Xiang-Yu Zhao, M.D.

Role: CONTACT

zhao_xy@bjmu.edu.cn

8610-88325949

Other Identifiers

2019PHD005-01

Identifier Type: -

Identifier Source: org_study_id