Clinical trial NCT04846439: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Platelet Transfusion Refractoriness
Acute Leukemia in Remission
Keywords: CAR-T
alloimmune
platelet transfusion refractoriness
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: The Second People's Hospital of Huai'an
name: The First Affiliated Hospital with Nanjing Medical University
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
First posted: 2021-04-15
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of Subjects With Sustained Platelet Transfusion Responsiveness
timeFrame: 12 months
measure: Adverse events after sequential infusion of CAR-T
timeFrame: 12 months
Secondary outcomes:
measure: B lymphocytes/plasma cell clearance
timeFrame: 12 months
measure: Amplification,distribution and persistence of CAR T-cells in vivo
timeFrame: 12 months
measure: Alloimmune antibodies(include HLA and HPA) in PB after sequential transfusion
timeFrame: 12 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Haiping Dai, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: