Anti-BCMA CAR T-Cell Therapy for R/R ITP

Anti-BCMA CAR T-Cell Therapy for Relapsed/Refractory Immune Thrombocytopenia

This is a prospective, single-center, open-label, single-arm study, to evaluate the efficacy and safety of Anti-BCMA chimeric antigen receptor T cell therapy（BCMA CAR-T）for patients with relapse/refractory Immune thrombocytopenia(R/R ITP).

Study Overview

• Status: Recruiting
• Conditions: ITP
• Intervention / Treatment: Biological: autologous anti-BCMA chimeric antigen receptor T cells

Detailed Description

Immune thrombocytopenia (ITP) is a disorder that can lead to easy or excessive bruising and bleeding. Approximately two-thirds of patients achieve remission after/during first-line therapies. However, the other part of patients could not achieve durable remission or even refractory to initial treatments. Those cases, known as relapse/refractory Immune thrombocytopenia (R/R ITP), undergo the heavy burden of disease which decreases the quality of life. Lots of pathogeneses take part in the occurrence of R/R ITP, and the most important one of them is antibody-mediated immune platelet destruction. As far as it is known，human platelet autoantibodies are mainly secreted by plasma cells, especially long-lived plasma cells. Researchers want to explore that can BCMA CAR-T help R/R ITP patients increase platelet count, reduce bleeding episodes and the dose of concomitant medications.

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, Ph.D; Phone Number: 86-512677801856; Email: xwtang1020@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refractory ITP defined according to the recent consensual criteria ( 'Chinese guideline on the diagnosis and management of adult primary immune thrombocytopenia (version 2020)'), or relapse ITP defined as ITP patients who have responded to first-line therapy (glucocorticoids or immunoglobulins) and anti-CD20 monoclonal antibody, but cannot maintain the response.
• Ages 18-65 years inclusive.
• Adequate venous access for apheresis or venous blood and no other contraindications for leukocytosis.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Subjects should have full capacity for civil conduct, understand necessary information，sign the informed consent form voluntarily，and have good corporation with the content of this research protocol.

Exclusion Criteria:

• Secondary ITP.
• Patients with a known history or prior diagnosis of arterial thrombosis (such as cerebral thrombosis, myocardial infarction, etc.), or comorbidity of venous thrombosis (such as deep vein thrombosis, pulmonary embolism), or are using anticoagulant/antiplatelet drug at the beginning of trial.
• Patients with a known history or prior diagnosis of serious cardiovascular disease.
• Patients with uncontrolled infection, organ dysfunction or any uncontrolled active medical disorder that would preclude participation as outlined.
• Patients with malignancy or history of malignancy.
• Failed T cell expansion test.
• During screening, hemoglobin <100g/L; absolute value of neutrophil count <1.5×10^9/L.
• During screening, serum creatinine concentration > 1.5x the upper limit of the normal range, total bilirubin > 1.5x the upper limit of the normal range, alanine aminotransferase and aspartate aminotransferase > 3x the upper limit of the normal range, Left ventricular ejection fraction ≤ 50% by echocardiography, Pulmonary function ≥ grade 1 dyspnea (CTCAE v5.0), blood oxygen saturation<91% without oxygen inhalation.
• Prothrombin time (PT) or prothrombin time-international normalized ratio (PT-INR) or activated partial thromboplastin time (APTT) exceeding 20% of the normal reference range; or a history of coagulation abnormalities other than ITP.
• Either HIV antibody or syphilis antibody is positive; hepatitis C antibody is positive and the detection of HCV-RNA exceeds the laboratory test upper reference limit; hepatitis B surface antigen is positive and the detection of HBV-DNA exceeds the laboratory test upper reference limit.
• Participated in other clinical studies within 3 months before this CAR-T cell infusion.
• Patients is pregnant or breastfeeding, or planning pregnancy.
• Patients is fertile and the investigator determines the case is inappropriate to participate.
• History of severe drug allergy or known allergy to CAR-T treatment related drugs.
• Suspected or established alcohol, drug or drug abuse.
• The investigator judges that it is not suitable to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Anti-BCMA CAR T-cells infusion; R/R ITP patients will accept infusion of autologous anti-BCMA CAR T-cells with a total of 1.0-2.0×10e7/Kg. The patients will be follow-up for 6 months post CAR T-cell therapy.

Biological: autologous anti-BCMA chimeric antigen receptor T cells; Lymphoadenodepletion chemotherapy with FC (fludarabine 30mg/ m2 for 3 consecutive days and cyclophosphamide 300mg/m2 for 3 consecutive days) will be given at day -5, -4 and -3 before CAR T-cells infusion. A total of 1.0-2.0×10e7/Kg autologous anti-BCMA CAR T-cells will be infused by dose-escalation after the lymphoadenodepletion chemotherapy. Dose of CAR T-cells are allowed to be adjusted according to the severity of cytokine release syndrome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response	The number of participants who achieved CR (defined as platelet count≥100x10e9/L) and PR (defined as platelet count ≥30x10e9/L and at least a 2-fold increase the baseline count and absence of bleeding) at follow-up.	6-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response	Time since infusion of CAR T-cells to the time to achieve the response.	6-months
Duration of response	Period from the achievement of response to the loss of response.	6-months
Incidence of adverse events	Adverse events will be assessed daily during the first 2 weeks after the BCMA CAR-T treatment, and monthly thereafter. Adverse events will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6-months
Evaluation of bleeding events	Bleeding events will be evaluated according to Bleeding rating system of ITP('Chinese guideline on the diagnosis and management of adult primary immune thrombocytopenia (version 2020)').	6-months
Evaluation of concomitant therapy	Duration of discontinuation or dose reduction of concomitant treatment，and the degree of decrease of combined treatment from the baseline in patients.	6-months
Evaluation of health-related quality of life	Health-related quality of life will be evaluated according to ITP-PAQ (Primary Immune Thrombocytopenia Patient Assessment Questionnaire).	6-months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; BCMA
• Other Study ID Numbers: BCRITP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No