Clinical trial NCT06223646: A Study of KQ-2003 CAR-T Cell Therapy for Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1/2a Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetic Characterization of KQ-2003 for Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-25
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, dose-escalation/expansion phase 1/2a study to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics and determine the recommended dose of KQ-2003 CAR T-cells for patients with Relapsed/Refractory Multiple Myeloma


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years old, male or female;
* Diagnosis of MM with relapsed or refractory disease;
* Eastern Cooperative Oncology Group (ECOG) Performance ≤2 ;
* Expected survival of at least 12 weeks;
* Participant has measurable disease;
* Adequate venous access for the apheresis of peripheral blood mononuclear cell;
* Adequate organ function;
* Able and willing to comply with the study protocol and follow-up plan, and sign the informed consent form in writing.

Exclusion Criteria:

* Received any treatment that might influence the activity of CAR-T cells prior to the collection of peripheral blood mononuclear cells;
* Have history of vaccination within the 4 weeks preceding the collection of peripheral blood mononuclear cells;
* Have active bleeding or venous thromboembolic events requiring anticoagulation;
* Have tested positive for cytomegalovirus and/or mycobacterium tuberculosis, or had any uncontrolled active infection within 14 days prior to the collection of peripheral blood mononuclear cells;
* Subjects infected with active HBV or HCV, HIV, syphilis;
* Subjects with known central nervous system disease or multiple myeloma involving the central nervous system (CNS) or presenting with CNS-related symptoms;
* Patients currently experiencing active autoimmune diseases;
* Diagnosed with immunodeficiency or receiving any other form of immunosuppressive therapy within 7 days prior to enrollment in this study.
* Have following severe diseases: unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction , New York Heart Association (NYHA) Class ≥ III, congestive heart failure, poorly controlled severe arrhythmias or other cardiac diseases requiring mechanical support; subjects with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal; subjects with known moderate or severe persistent asthma, or a history of asthma within the past 2 years, or currently having any category of uncontrolled asthma; subjects requiring oxygen to maintain adequate oxygen saturation; subjects with hypertension whose blood pressure cannot be lowered to the following range despite treatment with two or more antihypertensive medications;.
* Subjects with malignancies other than multiple myeloma;
* Have any non-hematologic toxicity resulting from prior treatments that cannot be restored to ≤ grade 1 or baseline, excluding alopecia and grade 2 neuropathy;
* History of alcohol abuse, drug addiction, substance abuse, or mental illness within the past year;
* Presence of acute graft-versus-host disease (GVHD) or extensive chronic GVHD of Grade ≥ 2 requiring treatment within the 4 weeks before enrollment, or as judged by the investigator to likely require anti-GVHD treatment during the study; Subjects who had previously received BCMA-CD19 dual-target CAR-T cell products or autologous stem cell transplantation within 12 weeks before the collection of peripheral blood mononuclear cells;
* Known allergy or hypersensitivity reactions to cyclophosphamide, fludarabine, dimethyl sulfoxide (DMSO), CD19, or BCMA-targeted drugs;
* Subjects had participated in other clinical trials and used its investigational drugs within the 3 months prior to the collection of peripheral blood mononuclear cells
* Pregnant or lactating women
* Any situation that the investigator believes may increase the risk of subjects or interfere with the results of clinical trials

Primary outcomes:
measure: Number of patients with dose-limiting toxicity (DLT)
timeFrame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within 28 days of receiving KQ-2003 CAR T-cells transfusion therapy
measure: Adverse Event
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Through study completion, an average of 1 year
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Stringent complete response rate (sCRR)
timeFrame: Through study completion, an average of 2 years
measure: Duration of Response (DOR)
timeFrame: Through study completion, an average of 2 years
measure: Disease Control Rate (DCR)
timeFrame: Through study completion, an average of 2 years
measure: Progression-free Survival (PFS)
timeFrame: Through study completion, an average of 2 years
measure: Overall Survival (OS)
timeFrame: Through study completion, an average of 2 years
measure: Microscopic Residual Disease (MRD) Negativity Rate and Duration
timeFrame: Through study completion, an average of 2 years
measure: Maximum concentration (Cmax)
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Time to maximum plasma concentration (Tmax)
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IL-6
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Levels of IFN-γ
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD4+T lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: CD8+T lymphocyte count
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: ADA
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
measure: Nab
timeFrame: Minimum 2 years after KQ-2003 CAR T-cells infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
Study officials:
References: