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

• Sponsor: Zhejiang University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04662788
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 72
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancies	Drug: NK cells/Combined Monoclonal Antibodies	Early Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Trial for the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies
• Anticipated Study Start Date: Jan 1, 2021
• Anticipated Primary Completion Date: Jan 1, 2024
• Anticipated Study Completion Date: Jan 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Dose-limiting toxicity (DLT) [Baseline up to 28 days after NK cells/Combined Monoclonal Antibodies infusion]

   Adverse events assessed according to NCI-CTCAE v5.0 criteria

2. Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after NK cells/Combined Monoclonal Antibodies infusion]

   Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

1. Acute Myeloid Leukemia (AML), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]

   Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24

2. AML, Overall survival (OS) [Up to 2 years after NK cells infusion]

   From the first infusion of NK cells/Combined Monoclonal Antibodies to death or the last visit

3. AML, Event-free survival (EFS) [Up to 2 years after NK cell/ Combined Monoclonal Antibodies infusion]

   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

4. Quality of life [At Baseline, Month 1, 3, 6, 9 and 12]

   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

5. Activities of Daily Living (ADL) score [At Baseline, Month 1, 3, 6, 9 and 12]

   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

6. Instrumental Activities of Daily Living (IADL) score [At Baseline, Month 1, 3, 6, 9 and 12]

   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

7. Hospital Anxiety and Depression Scale (HADS) score [At Baseline, Month 1, 3, 6, 9 and 12]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

3. CR not achieved after standardized chemotherapy;

4. CR achieved following the first induction, but CR duration is less than 12 months;

5. Ineffectively after first or multiple remedial treatments;

6. 2 or more relapses;

7. The number of primordial cells in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);

8. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;

9. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

10. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

11. Estimated survival time ≥ 3 months;

12. ECOG performance status 0 to 2;

13. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China

Sponsors and Collaborators

• Zhejiang University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: He Huang, Clinical Professor, Zhejiang University
• ClinicalTrials.gov Identifier: NCT04662788
• Other Study ID Numbers: NK-001
• First Posted: Dec 10, 2020
• Last Update Posted: Dec 10, 2020
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Antibodies; Antibodies, Monoclonal

Study Results

No Results Posted as of Dec 10, 2020