B-cell Lymphoma, B-cell Acute Lymphoblastic Leukemia
Conditions
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.
Interventions
DRUGQN-019a
Experimental Interventional Therapy
DRUGRituximab
Monoclonal Antibody
DRUGCyclophosphamid
Lympho-conditioning Agent
DRUGFludarabine
Lympho-conditioning Agent
DRUGVP-16
Lympho-conditioning Agent
Sponsors
Hangzhou Qihan Biotech Co.,Ltd.
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| 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 |
| 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 | — |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed