Natural Killer (NK) Cell Therapy for B-Cell Malignancies
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QN-019a in Combination with Monoclonal Antibodies QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. |
Drug: QN-019a
Experimental Interventional Therapy
Drug: Rituximab
Monoclonal Antibody
Drug: Cyclophosphamid
Lympho-conditioning Agent
Drug: Fludarabine
Lympho-conditioning Agent
Drug: VP-16
Lympho-conditioning Agent
|
| Experimental: QN-019a Monotherapy QN-019a Monotherapy in adult subjects with r/r B-ALL |
Drug: QN-019a
Experimental Interventional Therapy
Drug: Cyclophosphamid
Lympho-conditioning Agent
Drug: Fludarabine
Lympho-conditioning Agent
Drug: VP-16
Lympho-conditioning Agent
|
Outcome Measures
Primary Outcome Measures
- The incidence of subjects with Dose Limiting Toxicities within each dose level cohort [Day 28]
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Day 28]
Incidence, nature, and severity of treatment related adverse events will be evaluated.
Secondary Outcome Measures
- 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]
- 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]
- 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]
- 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]
- Determination of the pharmacokinetics (PK) of QN-019a cells in peripheral blood [Up to approximately 2 years after last dose of QN-019a]
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
- 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]
Eligibility Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Medical College of Zhejiang University | Hangzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- Zhejiang University
- Hangzhou Qihan Biotech Co.,Ltd.
Investigators
- Principal Investigator: He Huang, PhD, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NK-002 (QN-019a)