Clinical trial NCT04662788: Clinical Study on the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies
Official title: Clinical Trial for the Safety and Effectiveness of NK Cells/Combined Monoclonal Antibodies in the Treatment of Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2020-12-10
Enrollment: 36
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after NK cells/Combined Monoclonal Antibodies infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after NK cells/Combined Monoclonal Antibodies infusion
Secondary outcomes:
measure: Acute Myeloid Leukemia (AML), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: AML, Overall survival (OS)
timeFrame: Up to 2 years after NK cells infusion
measure: AML, Event-free survival (EFS)
timeFrame: Up to 2 years after NK cell/ Combined Monoclonal Antibodies infusion
measure: Quality of life
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: