A Clinical Study to Evaluate the Safety and Preliminary Efficacy of QI-019A in Patients With Relapsed/Refractory Multiple Myeloma.
Overview
- Phase
- Early Phase 1
- Status
- Not yet recruiting
- Sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- The number and severity of dose-limiting toxicity (DLT)events
Overview
Brief Summary
This is a single-arm, open-label, single-center clinical trial to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of QI-019A in patients with relapsed/refractory multiple myeloma.
Detailed Description
This investigator-initiated clinical study aims to evaluate QI-019A, the lentiviral vector that carries a BCMA/CD19-targeted CAR, in patients with relapsed or refractory multiple myeloma (MM). The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1\. Age ≥ 18 years, any gender;
- •2\. Diagnosed with multiple myeloma (MM) according to IMWG diagnostic criteria;
- •3\. Have received at least 2 lines of anti-MM treatment, with at least one full treatment cycle per line, and experienced disease progression during the most recent anti-myeloma treatment or within 12 months after it, confirmed by available clinical evidence; or deemed by the investigator to be refractory to both immunomodulatory agents and proteasome inhibitors, with disease progression during the most recent anti-myeloma treatment or within 2 months after it (according to IMWG diagnostic criteria);
- •4\. Disease must be measurable at screening, meeting one or more of the following criteria:
- •Serum M protein level ≥ 0.5 g/dL;
- •Or urine M protein level ≥ 200 mg/24h;
- •Or involved serum free light chain ≥ 10 mg/dL with abnormal serum free light chain κ/λ ratio;
- •5\. ECOG performance status 0-2, with an expected survival of ≥ 3 months;
- •6\. Bone marrow function test results (from screening or within 2 months prior) meet the following requirements:
- •Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week before screening), recombinant human erythropoietin allowed; for patients meeting the ≥ 6 g/dL hemoglobin requirement at screening, red blood cell transfusions are allowed to maintain hemoglobin ≥ 6 g/dL;
Exclusion Criteria
- •1.During screening, participants who have received other anticancer treatments (based mainly on investigator judgment):
- •Received targeted therapy, epigenetic therapy, other investigational drugs, or treatment using invasive research medical devices within 5 half-lives;
- •Received immune/non-immune-directed systemic therapy within 1 week;
- •Received cytotoxic therapy within 2 weeks;
- •Received proteasome inhibitors within 2 weeks;
- •Received immunomodulatory therapy within 1 week.
- •Received radiotherapy within 4 weeks (if the radiotherapy covered ≤5% of bone marrow reserve, the subject is eligible regardless of the radiotherapy end date);
- •2\. Received allogeneic hematopoietic stem cell transplantation within 6 months or autologous hematopoietic stem cell transplantation within 3 months before infusion;
- •3\. Had malignancies other than MM before screening, except for: malignancies treated with curative intent, with no known active disease ≥2 years prior to enrollment; or adequately treated non-melanoma skin cancer with no evidence of disease currently;
- •4\. Received any treatment using vesicular stomatitis virus G (VSVG) pseudotyped virus;
Arms & Interventions
QI-019A Injection
QI-019A Injection is an in vivo administered CAR-T gene therapy product that uses a lentiviral vector as the delivery system. Its mechanism of action involves transducing and integrating into the target T cell genome in the patient through the lentiviral vector, achieving stable expression of the CAR transgene, thereby generating CAR-T cells within the body.
Intervention: QI-019A Injection (Drug)
Outcomes
Primary Outcomes
The number and severity of dose-limiting toxicity (DLT)events
Time Frame: Within 28 Days After QI-019A infusion
Dose-limiting toxicity (DLT) refers to a grade ≥3 toxic reaction that occurs within the DLT observation period and is considered by the investigator or collaborators to have a reasonable association with QI-019A treatment (toxicity grading is based on CTCAE 5.0 standards, while grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) follows the 2019 ASTCT consensus criteria).
The total number, incidence, and severity of Adverse Events(AEs)
Time Frame: Within 28 Days After QI-019A infusion
The total number, incidence, and severity of Adverse Events(AEs). All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Secondary Outcomes
- Overall response rate (ORR）(Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A)
- Complete response (CR) rate(Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A.)
- Duration of response (DOR)(Through study completion, an average of 2 year)
- Progression-free survival (PFS)(up to 2 years after treatment of QI-019A.)
- Overall survival (OS)(up to 2 years after treatment of QI-019A)
- Cmax(Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A)
- Tmax(Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of QI-019A)
- AUC(0-day 28)(Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28 after the treatment of QI-019A)
Investigators
MEI HENG
Professor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology