Clinical Study on the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies

Clinical Trial for the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies

Clinical study on the safety and effectiveness of NK cells/combined monoclonal antibodies in the treatment of hematological malignancies

Study Overview

• Status: Not yet recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: NK cells/Combined Monoclonal Antibodies

Detailed Description

This is a single arm, open-label, single-center study. This study is indicated for hematological malignancies. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 36 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed diagnosis of AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);

2. Relapsed or refractory AML (meeting one of the following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is less than 12 months;
   3. Ineffectively after first or multiple remedial treatments;
   4. 2 or more relapses;
3. The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
4. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
5. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
6. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
7. Estimated survival time ≥ 3 months;
8. ECOG performance status 0 to 2;
9. Patients or their legal guardians volunteer to participate in the studyand sign the informed consent.

Exclusion Criteria:

1. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
7. Previously treated with any CAR-T cell product or other genetically- modified T cell therapies;
8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.

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: Administration of NK cells/Combined Monoclonal Antibodies	Drug: NK cells/Combined Monoclonal Antibodies; Each subject receive NK cells/Combined Monoclonal Antibodies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after NK cells/Combined Monoclonal Antibodies infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after NK cells/Combined Monoclonal Antibodies infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activities of Daily Living (ADL) score	Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Instrumental Activities of Daily Living (IADL) score	Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score	Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Quality of life	Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Acute Myeloid Leukemia (AML), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
AML, Overall survival (OS)	From the first infusion of NK cells/Combined Monoclonal Antibodies to death or the last visit	Up to 2 years after NK cells infusion
AML, Event-free survival (EFS)	From the first infusion of NK cells/Combined Monoclonal Antibodies to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit	Up to 2 years after NK cell/ Combined Monoclonal Antibodies infusion

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2027

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: NK-001

Drug and device information, study documents

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