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

NCT04846439 | Unknown Phase 1

• 1 other identifier: 2021062
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Platelet Transfusion Refractoriness; Acute Leukemia in Remission

Keywords

CAR-T; alloimmune; platelet transfusion refractoriness

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• B lymphocytes/plasma cell clearance

  12 months

• Amplification,distribution and persistence of CAR T-cells in vivo

  12 months

• Alloimmune antibodies(include HLA and HPA) in PB after sequential transfusion

  12 months

Study Arms (1)

CAR-T infusion

EXPERIMENTAL

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

Interventions

CAR-T infusion BIOLOGICAL

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.

CAR-T infusion

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

MeSH Terms

Interventions

Immunotherapy, Adoptive

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Haiping Dai, Ph.D

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaowen Tang, Ph.D

CONTACT

(0086)51267781856; xwtang1020@163.com

Study Design

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

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 15, 2021
• Study Start: April 29, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2024
• Last Updated: October 27, 2021

Record last verified: 2021-04

Locations

CN (1)