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

Hematological Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04662788
• Other study ID #: NK-001
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: January 1, 2021
• Est. completion date: January 1, 2027

Study information

• Verified date: December 2020
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Drug:
• NK cells/Combined Monoclonal Antibodies
Each subject receive NK cells/Combined Monoclonal Antibodies

Locations

Country	Name	City	State
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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