Natural Killer (NK) Cell Therapy for B-Cell Malignancies
- Conditions
- B-cell LymphomaB-cell Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT05379647
- Lead Sponsor
- Zhejiang University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description QN-019a Monotherapy QN-019a QN-019a Monotherapy in adult subjects with r/r B-ALL QN-019a in Combination with Monoclonal Antibodies QN-019a QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. QN-019a in Combination with Monoclonal Antibodies Cyclophosphamid QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. QN-019a Monotherapy Cyclophosphamid QN-019a Monotherapy in adult subjects with r/r B-ALL QN-019a Monotherapy Fludarabine QN-019a Monotherapy in adult subjects with r/r B-ALL QN-019a Monotherapy VP-16 QN-019a Monotherapy in adult subjects with r/r B-ALL QN-019a in Combination with Monoclonal Antibodies Rituximab QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. QN-019a in Combination with Monoclonal Antibodies Fludarabine QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma. QN-019a in Combination with Monoclonal Antibodies VP-16 QN-019a in Combination with Rituximab in adult subjects with r/r B-cell lymphoma.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (1)
The First Affiliated Hospital of Medical College of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China