CAR-T Cell Therapy Targeting to CD19 for R/R ALL

Acute Lymphoblastic Leukemia With Failed Remission Clinical Trial

Official title:

CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03919240
• Other study ID #: SZ4601
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 1, 2015
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2019
• Source: The First Affiliated Hospital of Soochow University
• Contact: Jia Chen, M.D., Ph.D.
• Phone: +86 512 67781856
• Email: drchenjia[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct a trial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosed as CD19+ B-cell acute lymphoblastic leukemia;

• Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation;

• With an estimated survival of higher than 3 months (according to investigator's judgement);

• Sufficient organ function: left ventricular ejection fractions= 0.5 by echocardiography, creatinine < 1.6 mg/dL, aspartate aminotransferase/aspartate aminotransferase < 3 x upper limit of normal, bilirubin <2.0 mg/dL;

• Karnofsky performance status = 60 or ECOG = 2.

Exclusion Criteria:

• Intolerant to immunosuppressive chemotherapies;

• With active infection or other uncontrolled complications;

• With history of seizure;

• Active hepatitis B or hepatitis C infection and HIV infection;

• Pregnant or lactating women, or patients refusing to take effective contraception measures;

• Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia With Failed Remission
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CAR T-cell therapy
Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5~10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

Country where clinical trial is conducted

China, 

References & Publications (1)

Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. Erratum in: Blood. 2015 Aug 20;126(8):1048. Dosage error in article text. Blood. 2016 Sep 15;128(11):1533. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission	defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery	1 month post infusion
Primary	Minimal residual disease response	defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection	1 month post infusion
Primary	Cytokine release syndrome	grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195). This grading system ranges from grade 1 (best) to grade 5 (worst), by measuring related symptoms (such as fever, nausea, fatigue, headache, etc.), oxygen requirement, blood pressure and organ toxicity (referred to CTCAE v4.0 grading)	1 month post infusion
Secondary	Overall survival	calculating from the day of CAR T-cell infusion to death or the end of follow-up	1 year post infusion
Secondary	Leukemia-free survival	calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up	1 year post infusion
Secondary	Cumulative incidence of relapse	calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up	1 year post infusion