Clinical trial NCT05379647: Natural Killer (NK) Cell Therapy for B-Cell Malignancies
Official title: QN-019a as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies in Subjects With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: B-cell Lymphoma
B-cell Acute Lymphoblastic Leukemia
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Hangzhou Qihan Biotech Co.,Ltd.
First posted: 2022-05-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The incidence of subjects with Dose Limiting Toxicities within each dose level cohort
timeFrame: Day 28
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Day 28
Secondary outcomes:
measure: 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
timeFrame: From baseline tumor assessment up to approximately 2 years after last dose of QN-019a
measure: 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
timeFrame: Up to approximately 2 years after last dose of QN-019a
measure: Progression-free survival (PFS) of QN-019a in combination with Rituximab in r/r B-cell Lymphoma
timeFrame: Up to approximately 2 years after last dose of QN-019a
measure: Overall survival (OS) of QN-019a as monotherapy in r/r B-ALL and in combination with Rituximab in r/r B-cell Lymphoma
timeFrame: Up to approximately 2 years after last dose of QN-019a
measure: Determination of the pharmacokinetics (PK) of QN-019a cells in peripheral blood
timeFrame: Up to approximately 2 years after last dose of QN-019a
measure: Event-free survival (EFS) of QN-019a as monotherapy in r/r B-ALL
timeFrame: Up to approximately 2 years after last dose of QN-019a
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Medical College of Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, PhD
role: PRINCIPAL_INVESTIGATOR
References: