CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia, Adult B-Cell Clinical Trial

Official title:

Evaluation of Safety and Efficacy of CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia Concomitant With Infusion of CD19+T Cells as Feeding Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03984968
• Other study ID #: SZCART01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 1, 2018
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: The First Affiliated Hospital of Soochow University
• Contact: Sheng-Li Xue, M.D.
• Phone: +86 512 67781139
• Email: slxue[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm, open-label, single-center, phase I/II study to determine the safety and efficacy of CD19 CAR-T( ssCART-19) combined with feeding T cells (FTCs) as consolidation therapy in patients diagnosed with de novo Philadelphia chromosome positive CD19+ B-ALL. The study will contain the following sequential phases: screening, lymphocyte apheresis, induction and consolidation chemotherapies combined with tyrosine kinase inhibitors. Once in complete response, patients will receive four cycles of ssCART-19s, namely one cycle of ssCART-19 infusion followed by another three cycles of ssCART-19 and FTC infusion. The role of FTCs is to mimic leukemia cells. Therefore, they are expected to stimulate in vivo expansion and persistence of ssCART-19. Considering the limited number of lymphocytes obtained by a single apheresis from patients and cost-efficacy, in addition to safety, we will explore the range of biologically active doses of FTCs in a phase I study. Based on preclinical data, FTCs stimulation of ssCART-19 at a ratio of 1:1 could achieve the best activation response, so 5×106/kg dosage of FTCs was set as the initial dosage in the study, and lower dose was also evaluated. In this study, FTCs will be administered at the dose of 5×106/kg, 3.25×106/kg or 2×106/kg two hours after ssCART-19 infusion on day 1 and once again administered at the same dose on day 8. After ssCART-19 and FTCs infusion, efficacy will be assessed by detecting molecular response for 6 months, PFS and OS will be followed up for 2 years. In phase II, we will expand the study at optimal biological doses of FTCs, and further evaluate the efficacy and safety of the innovative combination therapy of CD19 CAR-T and FTCs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Ph+ acute B-lymphoblastic leukemia patients having received once CD19 CAR-T therapy

• continuously taking TKI medications

• no chance to receive allogeneic hematopoietic stem cell transplantation

• no severe complications

• ECOG score less than 3

Exclusion Criteria:

• Detection of mutations on abl gene

• resistance to TKI medications

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, Adult B-Cell
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CD19 CAR-T cells infusion combined with feeding T cells (FTCs)
Phase1 study Optimal biological doses of feeding T cells identification CAR-T cells infusion combined with FTCs will be given in Philadelphia chromosome positive B-ALL patients with remission. FTCs will be administered at the dose of 5×106/kg, 3.25×106/kg or 2×106/kg two hours after ssCART-19 infusion on day 1 and once again administered at the same dose on day 8. Phase 2 Expansion Study CAR-T cells infusion combined with FTCs at optimal biological dosage determined in Phase 1 study will be given in expanded Philadelphia chromosome positive B-ALL patients with remission. Bayesian optimal design is applied in this Phase 2 study to monitor the toxicity and efficacy at the specified interim analyses. The total expected sample sizes are 40.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase1 Incidence of adverse events (AEs) and abnormal laboratory test results	AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).	6 months after CD19 CAR-T consolidation therapy termination
Primary	Phase 2 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells.	Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.	3 months after CD19 CAR-T consolidation therapy termination
Secondary	Phase 1 Molecular response after CD19 CAR-T consolidation therapy for acute Lymphoblastic Leukemia concomitant with infusion of feeding Cells.	Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.	3 months after CD19 CAR-T consolidation therapy termination
Secondary	Phase 1 The range of biologically active doses and optimal biological doses of feeding T cells.	The range of biologically active doses and optimal biological doses of feeding T cells will be determined.	6 months after CD19 CAR-T consolidation therapy termination
Secondary	Phase 1 Overall survial (OS)	It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	2 years
Secondary	Phase 1 Relapse free survival(RFS)	It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.	2 years
Secondary	Phase 2 Incidence of adverse events (AEs) and abnormal laboratory test results	AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).	6 months after CD19 CAR-T consolidation therapy termination
Secondary	Phase 2 Overall survial (OS)	It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	2 years
Secondary	Phase 2 Relapse free survival(RFS)	It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.	2 years