Sequential Infusion of CD19 and BCMA CAR-T Cells to Improve PTR in Patients With AL

Sequential Infusion of CD19 and BCMA Chimeric Antigen Receptor T Cells to Improve Alloimmune-mediated Platelet Transfusion Refractoriness in Patients With Acute Leukemia in Complete Remission

Alloimmune-mediated platelet transfusion refractoriness(PTR) was usually caused by repeated blood transfusions and pregnancy and accounts for about 20-25% of PTR patients. Patients with acute leukemia need repeated platelet infusion in myelosuppression period after chemotherapy, and PTR incidence is more higher.PTR was associated with adverse events,including longer hospital stays,severe hemorrhages and an increased risk of early deaths and may have a negative impact on the success of HSCT. The current management of patients with PTR includes specific transfusion strategies, IVIG, rituximab,thrombopoietin-receptor agonists(TPO-RA) ,bortezomib or splenectomy,have been largely unsatisfactory. As we know, HLA antibodies are mainly secreted by the plasma cells. Researchers want to see if sequential infusion of CD19 and BCMA CAR-T cells can clear the B cells and plasma cells, can help increase platelet levels and reduce bleeding in patients with platelet transfusion refractoriness. To see if sequential infusion can increases platelet levels more after a transfusion. To see if it reduces the chance of bleeding. Adults 16-65 years old who diagnosed with acute leukemia in CR and alloimmune platelet transfusion refractoriness.

Study Overview

• Status: Recruiting
• Conditions: Platelet Transfusion Refractoriness; Acute Leukemia in Remission
• Intervention / Treatment: Biological: CAR-T infusion

Detailed Description

The patients will receive infusion of CAR T-cells targeting CD19 and BCMA to confirm the safety and efficacy of CD19 and BCMA CAR T-Cells Sequential infusion in acute leukemia with alloimmune-mediated platelet transfusion refractoriness.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 16-65 years inclusive.
• Ability to comprehend the investigational nature of the study and provide informed consent.
• Expected survival time ≥ 3 months (according to investigator's judgement)
• Acute leukemia in complete remission diagnosed with alloimmune-mediated PTR, characterized by all of the following:

Lack of adequate post-transfusion platelet count increment, defined by CCI <7500/μl at 10-60 min, and CCI <5000/μl at 18-24 hrs (in those who had a CCI at 10-60 min greater than or equal to 5000/μl) after at least 2 consecutive transfusions.

Presence of anti-HLA class A and/or B antibody.

• Left ventricular ejection fractions ≥ 0.5 by echocardiography.
• Creatinine < 1.6 mg/dL.
• Aspartate aminotransferase/aspartate aminotransferase < 3x upper limit of normal.
• Total bilirubin <2.0 mg/dL.
• karnofsky performance status ≥ 60.

Exclusion Criteria:

• PTR induced by other reasons(eg:DIC,fever,infection and splenomegaly)
• Uncontrolled active infection.
• Active hepatitis B or hepatitis C infection
• Patients with HIV or syphilis infection
• Patients are pregnant or lactating
• Patients has a history of allo-HSCT
• Alloimmune-mediated PTR responsive to treatment with plasma exchange
• Alloimmune-mediated PTR responsive to treatment with rituximab or IVIG
• Grade III/IV cardiovascular disability according to the New York Heart Association Classification
• Patients with other contraindications considered unsuitable for participation in this study (according to investigator's judgement)

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: CAR-T infusion; CD19 and BCMA CAR-T cells were infused into complete remission acute leukemia patients with PTR sequentially, with（1.0-2.0）×10e7/kg respectively. Each patient was followed up for 1 years.	Biological: CAR-T infusion; Sequential infusion of CD19 and BCMA autologous chimeric antigen receptor T cells, the infusion dose was determined according to the body weight of the subject and the effective content of cell preparation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Sustained Platelet Transfusion Responsiveness	To evaluate the safety and efficacy of sequential infusion of CD19 and BCMA CAR-T cells to improve PTR, estimate by platelet increment, defined as Corrected Count Increment (CCI) >7500/μL at 10-60 min together with CCI>5000/μL at 18-24 hrs post platelet transfusion in patients with platelet transfusion refractoriness.	12 months
Adverse events after sequential infusion of CAR-T	Adverse events are evaluated with CTCAE V5.0.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B lymphocytes/plasma cell clearance	To investigate the possible mechanisms of sequential infusion in alloimmune-mediated PTR	12 months
Amplification,distribution and persistence of CAR T-cells in vivo	To evaluate the persistence of CAR-T cells in vivo	12 months
Alloimmune antibodies(include HLA and HPA) in PB after sequential transfusion	To evaluate the clearance of alloimmune antibodies.	12 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; The Second People's Hospital of Huai'an; Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Investigators: Principal Investigator: Haiping Dai, Ph.D, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: CAR-T; alloimmune; platelet transfusion refractoriness
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: 2021062

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No