Natural Killer (NK) Cell Therapy for B-Cell Malignancies

B-cell Lymphoma Clinical Trial

Official title:

QN-019a as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies in Subjects With B-Cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05379647
• Other study ID #: NK-002 (QN-019a)
• Status: Recruiting
• Phase: Phase 1
• Start date: November 4, 2021
• Est. completion date: December 2024

Study information

• Verified date: May 2022
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, Phase I study of QN-019a (allogeneic CAR-NK cells targeting CD19) as monotherapy in relapsed/refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) and in combination with Rituximab in relapsed/refractory B-cell Lymphoma.

This clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-019a in patients with relapsed/refractory B-cell lymphoma or B-ALL. Up to 22-36 patients will be enrolled.

Description:

This is an open-label, Phase I study of QN-019a (allogeneic CAR-NK cells targeting CD19) as monotherapy in relapsed/refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) and in combination with Rituximab in relapsed/refractory B-cell Lymphoma.

This clinical study is to evaluate the safety, tolerability and preliminary efficacy of QN-019a in patients with relapsed/refractory B-cell lymphoma or B-ALL, where a "3+3" enrollment schema will be utilized at dose escalation stage. Up to 24-36 patients will be enrolled.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Diagnosis of B-cell lymphoma or B-ALL as described below:

B-cell Lymphoma:

• Histologically documented lymphomas expected to express CD19 and CD20

• Relapsed/refractory disease following at least two prior systemic treatment regimens, or relapsed after the autologous hematopoietic stem cell transplantation (HSCT)

B-ALL:

• Diagnosis of B-ALL that expected to express CD19

• Relapsed/refractory disease following prior systemic treatment regimens

ALL SUBJECTS:

• Provision of signed and dated informed consent form (ICF)

• Age = 18 years old

• Stated willingness to comply with study procedures and duration

• Eastern Cooperative Oncology Group (ECOG) performance status =1

• Adequate organ function as defined in the protocol

• Donor specific antibody (DSA) to QN-019a: MFI <= 2000

• At least 3 weeks after the last systemic immunochemotherapy treatment

• The estimated survival days are expected to be over 3 months

Key Exclusion Criteria:

ALL SUBJECTS:

• Females who are pregnant or lactating

• Evidence of insufficient organ function as defined in the protocol

• ECOG Performance Status =2

• Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T/CAR-NK within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy

• Currently receiving or likely to require systemic immunosuppressive therapy

• Known active central nervous system (CNS) involvement by malignancy. Non-malignant CNS disease such as stroke, epilepsy, or neurodegenerative disease

• Clinically significant cardiovascular disease as defined in the protocol

• Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection

• Donor specific antibody (DSA) to QN-019a: MFI > 2000

• Other comorbid conditions and concomitant medications prohibited as per study protocol

• Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• B-cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• QN-019a
Experimental Interventional Therapy
• Rituximab
Monoclonal Antibody
• Cyclophosphamid
Lympho-conditioning Agent
• Fludarabine
Lympho-conditioning Agent
• VP-16
Lympho-conditioning Agent

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Hangzhou Qihan Biotech Co.,Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of subjects with Dose Limiting Toxicities within each dose level cohort		Day 28
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence, nature, and severity of treatment related adverse events will be evaluated.	Day 28
Secondary	Objective response rate (ORR) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma		From baseline tumor assessment up to approximately 2 years after last dose of QN-019a
Secondary	Duration of response (DOR) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma		Up to approximately 2 years after last dose of QN-019a
Secondary	Progression-free survival (PFS) of QN-019a in combination with Rituximab in r/r B-cell Lymphoma		Up to approximately 2 years after last dose of QN-019a
Secondary	Overall survival (OS) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma		Up to approximately 2 years after last dose of QN-019a
Secondary	Determination of the pharmacokinetics (PK) of QN-019a cells in peripheral blood	The PK of QN-019a in peripheral blood will be reported as the relative percentage of product (QN-019a) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points	Up to approximately 2 years after last dose of QN-019a
Secondary	Event-free survival (EFS) of QN-019a as monotherapy in r/r B-ALL		Up to approximately 2 years after last dose of QN-019a