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

Primary Purpose

Platelet Transfusion Refractoriness, Acute Leukemia in Remission

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAR-T infusion
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Platelet Transfusion Refractoriness focused on measuring CAR-T, alloimmune, platelet transfusion refractoriness

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T infusion

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
Adverse events after sequential infusion of CAR-T
Adverse events are evaluated with CTCAE V5.0.

Secondary Outcome Measures

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

Full Information

First Posted
April 13, 2021
Last Updated
October 19, 2021
Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
The Second People's Hospital of Huai'an, The First Affiliated Hospital with Nanjing Medical University, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04846439
Brief Title
Sequential Infusion of CD19 and BCMA CAR-T Cells to Improve PTR in Patients With AL
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 29, 2021 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
The Second People's Hospital of Huai'an, The First Affiliated Hospital with Nanjing Medical University, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platelet Transfusion Refractoriness, Acute Leukemia in Remission
Keywords
CAR-T, alloimmune, platelet transfusion refractoriness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-T infusion
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CAR-T infusion
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Subjects With Sustained Platelet Transfusion Responsiveness
Description
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.
Time Frame
12 months
Title
Adverse events after sequential infusion of CAR-T
Description
Adverse events are evaluated with CTCAE V5.0.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
B lymphocytes/plasma cell clearance
Description
To investigate the possible mechanisms of sequential infusion in alloimmune-mediated PTR
Time Frame
12 months
Title
Amplification,distribution and persistence of CAR T-cells in vivo
Description
To evaluate the persistence of CAR-T cells in vivo
Time Frame
12 months
Title
Alloimmune antibodies(include HLA and HPA) in PB after sequential transfusion
Description
To evaluate the clearance of alloimmune antibodies.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaowen Tang, Ph.D
Phone
(0086)51267781856
Email
xwtang1020@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haiping Dai, Ph.D
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
xiaowen tang, Ph.D
Phone
(0086)51267781856
Email
xwtang1020@163.com

12. IPD Sharing Statement

Learn more about this trial

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

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