NK Cell Therapy for AML

NCT05256277 | Terminated Phase 1 DMC

• 1 other identifier: CT101a-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, non-randomized, multiple-dose, phase 1 dose escalation study evaluating the safety, efficacy and PK of CT101a in patients with relapsed/refractory acute myeloid leukemia. Primary Objective: To evaluate the safety and tolerability of CT101a and estimate the MTD in Chinese patients. Secondary Objective: To determine the preliminary efficacy of CT101a in the treatment of r/r AML by IWG response rate; To determine the duration of response, time to progression, disease-free survival, and overall survival of AML patients treated with CT101a. Exploratory Objective: To investigate and analyze the correlation between the donor KIR gene and the efficacy in the subject. To explore the feasibility and safety of multiple doses of CT101a in the treatment of r/r AML. To detect blood samples and bone marrow samples before and after CT101a infusion by single cell sequencing method, and to perform difference analysis.

Conditions

AML

Keywords

cytokine-induced memory-like NK cells; relapsed or refractory acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• DLT/MTD

  The severity of adverse events is graded according to NCI-CTCAE version 5.0, and the investigator will determine whether the subject has DLT. Taking into account the clinical characteristics of AML patients, DLT is defined as: During the 28-day DLT observation period after CT101a infusion, the subject still has any of the following conditions related to the study drug despite the treatment measures taken: 1\. Non-hematology related DLT: Any non-hematologic AE ≥ Grade 3 that is caused by CT101a treatment and does not resolve to below Grade 2 within 3 days; infusion-related reactions will not be considered as DLT. Patients with clinical progression of AML after CT101a infusion can receive cytoreductive therapy (such as hydroxyurea, cytarabine) to control their disease, and maintain the DLT assessment during the entire DLT period, but any AE related to cytoreductive therapy will not be considered as DLT.

  28 days

Secondary Outcomes (6)

• Safety parameters

  2 years

• overall response rate

  2 years

• DOR

  2 years

• OS

  2 years

• TTP

  2 years

Study Arms (1)

CT101a

EXPERIMENTAL

1 dose infusion

Drug: CT101a

Interventions

CT101a DRUG

cytokine-induced memory-like NK cells

CT101a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with relapsed or refractory AML:
• For patients with relapsed AML: after complete response (CR), leukemia cells or blast cells in the bone marrow reappear \>5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy).
• For patients with refractory AML: initial cases who have been treated with standard regimens for 2 courses of treatment that are not effective; after CR, they undergo consolidation and intensive treatment and relapse within 12 months; those who relapse after 12 months but are ineffective after conventional chemotherapy; those who relapse for 2 or multiple times.
• AML patients with disease progression after transplantation.
• Male or female ≥ 18 years old.
• ECOG Performance Status 0 to 2.
• Life expectancy ≥3 months.
• Available HLA-haploidentical donor meeting the following criteria:
• Related donor (parent, sibling, offspring, or offspring of sibling);
• At least 18 years of age;
• HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus;
• In general, the donor is healthy and can tolerate leukapheresis for collecting NK cells required in this study;
• Negative for HCV antibody, five items of HBV, HIV antibody and syphilis on donor viral screening;
• The female donor of childbearing potential must have a negative pregnancy test within screening.
• Voluntary written consent to participate in this study.

You may not qualify if:

• Acute or chronic GVHD with ongoing active systemic treatment.
• Circulating blast count \>30,000/μL by morphology or flow cytometry.
• Prior treatment with ML NK cell therapy within 3 months prior to screening.
• Patients who are undergoing any approved or investigational chemotherapy and anti-leukemic therapy with small molecule-targeted drugs within the 14 days prior to the first dose of fludarabine.
• Presence of any severe or uncontrolled systemic disease or condition.
• Patients with active infection requiring systemic therapy within 2 weeks prior to screening.
• HBsAg positive and HBV DNA is detectable or above the cut-off value or positive HCV antibody or positive HIV antibody or positive syphilis test.
• New progressive pulmonary infiltrates on screening chest X-ray or chest CT scan that have not been evaluated with bronchoscopy.
• Patients with a significant cardiovascular disease or condition.
• Inadequate bone marrow reserve or organ function.
• Other patients judged inappropriate for this study by the investigators.

Sponsors & Collaborators

• Zhejiang University: lead
• Shanghai Zeke Biotechnology Co.，Ltd: collaborator

Study Sites (1)

The First Affiliated Hospital，College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Huang He, PhD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 25, 2022
• Study Start: December 28, 2021
• Primary Completion: August 28, 2022
• Study Completion: April 3, 2023
• Last Updated: May 16, 2023

Record last verified: 2023-05

Locations

CN (1)