Efficacy and Safety of CAR-T Cells Therapy for Chronic or Refractory Primary Immune Thrombocytopenia (ITP)

Official title

An Investigator-initiated Trial to Evaluate the Efficacy and Safety of CAR-T Cells Therapy in the Treatment of Chronic or Refractory Primary Immune Thrombocytopenia (ITP)

Overview

It is a single-center, single-arm, open-labeled clinical trial to evaluate the efficacy and safety of CAR-T cells therapy for Chronic or Refractory Primary Immune Thrombocytopenia (ITP).

Detailed description

This open label and single-arm study aims to evaluate the efficacy and safety of CAR-T cells therapy in patients with Chronic or Refractory Primary Immune Thrombocytopenia (ITP). After enrollment, a leukapheresis procedure will be performed to manufacture chimeric antigen receptor (CAR) modified T cells. Patients will get a 3-5 days lymphodepletion therapy with fludarabine and cyclophosphamide, then the CAR-T cells will be infused by vein. After infusion, subjects will be followed for safety and efficacy evaluation up to 12 weeks. For those with a durable remission 12 weeks after infusion, the follow-up will last for at least 12 months for disease control.

Interventions

• Biological CAR-T cells
  CAR-T cells will be administered by vein. Before CAR-T infusion，patients will get a 3-5 days lymphodepletion therapy with fludarabine and cyclophosphamide.

Primary outcome measures

• Portion of patients with response (R) [Time frame: At least 2 weeks after infusion]

Secondary outcome measures (6)

• Portion of patients with complete response (CR) [Time frame: At least 2 weeks after infusion]
• Portion of patients with relapse [Time frame: At least 2 weeks after infusion]
• Time (in days) from treatment start to response (R) [Time frame: At least 2 weeks after infusion]
• Time (in days) from treatment to complete response (CR) [Time frame: At least 2 weeks after infusion]
• Duration (in days) of response (R) [Time frame: At least 2 weeks after infusion]
• Incidence of adverse events(AE) after infusion [Time frame: Up to 12 months after infusion]

Eligibility criteria

Inclusion criteria

• Willingness to complete the informed consent process and to comply with study procedures and visit schedule;
• Men and women aged 8-75;
• Participants diagnosed with chronic (>12 months duration) or refractory (a documented intolerance or insufficient response to the first and second line standard treatment of ITP) ITP;
• The results of physical, instrumental, and laboratory examination of patients not suggest any disease which may cause thrombocytopenia other than ITP;
• Platelet count <30 x 109 / L;
• If the patient is taking corticosteroids, the treatment regimen/dose should be stable (at least 2 weeks prior to screening);
• The results of physical, instrumental, and laboratory examination of patients should be within the normal range or deviations should be regarded by the researcher as clinically insignificant;
• Willingness to use effective and reliable methods of contraception throughout the entire study period;

Exclusion criteria

• All subjects with diseases which may cause secondary immune thrombocytopenia
• Patients with preventive splenectomy;
• Hemostatic disorders other than chronic thrombocytopenia;
• Subject treated with drugs that affect platelet function (including but not limited to aspirin, clopidogrel and/or NSAIDs) or anti-coagulants for > 3 consecutive days within 2 weeks of the study start and until the end of the study;
• History of platelet agglutination abnormality that prevents reliable measurement of platelet counts;
• Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy;
• Grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically prominent heart disease within one year prior to enrollment;
• History of thrombosis or presence of significant risk factors for thrombosis;
• Persons with acute or exacerbation of chronic diseases of the gastrointestinal tract associated with the risk of bleeding, acute infectious diseases, pathologies of the respiratory system;
• Any clinically significant hepatic impairment (increase of serum transaminase levels by more than 3 times the upper limit of normal);
• Serum creatinine levels are more than two times higher than the upper limit of normal for a given age and sex;
• Any other concomitant decompensated diseases or acute conditions, the presence of which, according to the researcher, may significantly affect the results of the study;
• Human immunodeficiency virus (HIV) seropositivity, Hepatitis B surface antigen positive or hepatitis B core antibody positive and HBV-DNA positive, Patients with hepatitis C (HCV-RNA quantitative test results positive), Or the presence of other serious active viral or bacterial infections or uncontrolled systemic fungal infections;
• Patients with severe history of allergy or allergic constitution;
• Pregnancy and lactation;
• History of mental illness and known alcohol/drug addiction;
• Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
• Had undergone other clinical trials in the 4 weeks prior to participating in this trial;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China — Kunming

Identifiers

NCT: NCT06352281 · KM-007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗