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

Acute Leukemia in Remission Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04846439
• Other study ID #: 2021062
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 29, 2021
• Est. completion date: March 31, 2024

Study information

• Verified date: April 2021
• Source: The First Affiliated Hospital of Soochow University
• Contact: Xiaowen Tang, Ph.D
• Phone: (0086)51267781856
• Email: xwtang1020[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Leukemia in Remission
• Leukemia
• Platelet Transfusion Refractoriness

Intervention

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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (5)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Huai'an Second People's Hospital, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Adverse events after sequential infusion of CAR-T	Adverse events are evaluated with CTCAE V5.0.	12 months
Secondary	B lymphocytes/plasma cell clearance	To investigate the possible mechanisms of sequential infusion in alloimmune-mediated PTR	12 months
Secondary	Amplification,distribution and persistence of CAR T-cells in vivo	To evaluate the persistence of CAR-T cells in vivo	12 months
Secondary	Alloimmune antibodies(include HLA and HPA) in PB after sequential transfusion	To evaluate the clearance of alloimmune antibodies.	12 months