A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed/ Refractory Multiple Myeloma

NCT06732232 | Recruiting Early Phase 1

• 1 other identifier: BZE2204-B-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologouschimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed/refractory multiple myeloma.

Conditions

Relapsed; Refractory; Multiple Myeloma

Keywords

relapsed/refractory multiple myeloma; CAR-T; CD19; CD22; BCMA

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity(DLT)

  Safety

  [Time Frame: Day0-Day28]

• Maximum tolerated dose (MTD)

  Evaluate the incidence, severity, and correlation of SAE Tolerability

  [Time Frame: Day0-Day28]

Secondary Outcomes (16)

• Maximum Plasma Concentration(Cmax)

  [Time Frame: Day0-Day28#Day0-undetectable for CAR positive T cells]

• Maximum Plasma Concentration Time (Tmax)

  [Time Frame: Day0-Day28#Day0-undetectable for CAR positive T cells]

• Area Under Curve (AUC)

  [Time Frame: Day0-Day28#Day0-undetectable for CAR positive T cells]

• CAR positive T cells

  [Time Frame: Day0-Day28#Day0-undetectable for CAR positive T cells]

• Cytokines ( IL(interleukin)-2）

  [Time Frame:Day0-Day28]

Study Arms (1)

CD19/CD20/BCMA CAR-T cells therapy

EXPERIMENTAL

CD19/CD20/BCMA CAR T cells Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CD19/CD20/BCMA CAR T cells. Cyclophosphamide and fludarabine will be given from day-5 to day-3 before the infusion for lymphodepletion. On day0 subjects will receive one dose treatment with CD19/CD20/BCMA CAR T cells by intravenous (IV) injection

Drug: CD19/CD20/BCMA CAR-T

Interventions

CD19/CD20/BCMA CAR-T DRUG

CD19/CD20/BCMA CAR T therapy

CD19/CD20/BCMA CAR-T cells therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria in order to be enrolled:
• Understand and voluntarily sign an informed consent form (ICF) before conducting any research related evaluations/procedures;
• Age range: 18-75 years old;
• Expected survival period is not less than 12 weeks;
• ECOG score ≤ 2 points;
• The bone marrow flow cytometry results showed positive BCMA antigen (including weak positive, moderate positive, and strong positive);
• According to the IMWG criteria, a diagnosis of multiple myeloma with measurable lesions must meet at least one of the following criteria:
• Serum M protein (SPEP) ≥ 5g/L
• hour urinary M-protein excretion rate ≥ 0.2g (200mg)
• Serum free light chain (sFLC) ≥ 100 mg/L and abnormal free light chain ratio
• The ratio of primitive plasma cells to immature plasma cells in bone marrow cytology examination is greater than 5%, or the flow cytometry detection of monoclonal plasma cells is greater than 5%
• Those who have received treatment with at least three different mechanisms of action (including anti-CD38 monoclonal antibodies, protease inhibitors, immunosuppressants, etc.) but have failed, and have experienced relapse (within 12 months), difficulty in treatment, or intolerance to the last line treatment regimen, including primary difficulty in treatment (subjects who have not achieved minimal remission \[MR\] or developed disease progression \[PD\] during treatment) or secondary difficulty in treatment (subjects who develop disease progression within 60 days after completion of treatment);
• There is no significant abnormality in lung function, and the oxygen saturation is greater than 92% in the absence of oxygen inhalation;
• The blood biochemistry test results meet the following criteria:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)

You may not qualify if:

• Any of the following situations cannot be selected as a subject:
• Asymptomatic (smoking type) multiple myeloma;
• Multiple myeloma with only extramedullary lesions present;
• Plasma cell leukemia;
• Merge amyloidosis;
• Central nervous system (CNS) metastasis, leptomeningeal disease, or metastatic central compression;
• Pregnancy or lactation period;
• Individuals who are HBsAg positive or HBcAb positive, unless HBV-DNA is less than 100 IU/ml or below the minimum detectable value; Individuals who are positive for hepatitis C virus (HCV) antibodies and HCV-RNA; Individuals who are HIV antibody positive; Individuals who are positive for syphilis specific antibodies and have a positive TRUST (toluidine red unheated serum test) test; Individuals who test positive for Cytomegalovirus (CMV) DNA;
• Cardiovascular diseases with clinical significance, including any of the following:
• QT interval (QTcF) after heart rate correction:\>470 milliseconds;
• New York Heart Association Grade II and above heart failure;
• Left ventricular ejection fraction (LVEF) ≤ 50%;
• Poorly controlled hypertension (systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 95 mm Hg)
• Arrhythmias that have clinical significance or require antiarrhythmic treatment (such as persistent ventricular tachycardia, ventricular fibrillation, apical torsion tachycardia, and complete left bundle branch block);
• Has experienced unstable angina or acute myocardial infarction within the 6 months prior to signing the ICF;

Sponsors & Collaborators

• Shanghai Cell Therapy Group Co.,Ltd: lead

Study Sites (1)

China, Shanghai Mengchao Cancer Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jinxing Lou

  China, Shanghai Mengchao Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinxing Lou

CONTACT

0086-021-67091399; loujx@shcell.com

Jinxing Lou

CONTACT

loujx@shcell.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 13, 2024
• Study Start: December 12, 2024
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2027
• Last Updated: December 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)