CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

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 autologous T cells engineered to express CD19, namely CD19+ 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 two to four cycles of ssCART-19s, namely one cycle of ssCART-19 infusion (CAR-T1) followed by one to three cycles of ssCART-19 and CD19+ FTC infusion (CAR-T2-4). The role of CD19+ 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 a 5×10\^6/kg dosage of FTCs was set as the initial dosage in the study, and lower doses were also evaluated. In phase I, FTCs will be administered at the dose of 5×10\^6/kg, 3.25×10\^6/kg, or 2×10\^6/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, adverse events (AEs) as the primary endpoints will be recorded for 6 months; efficacy as the secondary endpoint will be assessed by detecting molecular response for 6 months, PFS, and OS 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 ssCART-19 and FTCs. The primary endpoint was the complete molecular response (CMR). The secondary endpoints were RFS, OS, and adverse events (AEs) of the patients.

Conditions

• Acute Lymphoblastic Leukemia, Adult B-Cell

Interventions

BIOLOGICAL

ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Phase 1: Optimal biological doses of feeding T cells (FTCs) identification. ssCART-19 cells combined with CD19+ FTCs were administered to Philadelphia chromosome-positive B-ALL patients with remission. ssCART-19 was infused at the dose of 5×10\^6/kg on days 1 to 3 of the first cycle and on day 1 of the second to fourth cycle. CD19+ FTCs (5×10\^6 cells/kg) were infused two hours after the infusion of ssCART-19 cells on day 1 and at the same dose alone on day 8 of the second to fourth cycle. Five patients were enrolled in this arm, and all the patients received four cycles of ssCART-19 consolidation.

BIOLOGICAL

ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Phase 1: Optimal biological doses of feeding T cells (FTCs) identification. ssCART-19 cells combined with CD19+ FTCs were administered to Philadelphia chromosome-positive B-ALL patients with remission. ssCART-19 was infused at the dose of 5×10\^6/kg on days 1 to 3 of the first cycle and on day 1 of the second to fourth cycle. CD19+ FTCs (3.25×10\^6 cells/kg) were infused two hours after the infusion of ssCART-19 cells on day 1 and at the same dose alone on day 8 of the second to fourth cycle. Four patients were enrolled in this arm, and all the patients received four cycles of ssCART-19 consolidation.

BIOLOGICAL

ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Phase 1: Optimal biological doses of feeding T cells (FTCs) identification. ssCART-19 cells combined with CD19+ FTCs were administered to Philadelphia chromosome-positive B-ALL patients with remission. ssCART-19 was infused at the dose of 5×10\^6/kg on days 1 to 3 of the first cycle and on day 1 of the second to fourth cycle. CD19+ FTCs (2×10\^6 cells/kg) were infused two hours after the infusion of ssCART-19 cells on day 1 and at the same dose alone on day 8 of the second to fourth cycle. Four patients were enrolled in this arm, and all the patients received four cycles of ssCART-19 consolidation.

BIOLOGICAL

ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion

Phase 2: Expansion Study. ssCART-19 cells combined with FTCs at the optimal biological dosage determined in the Phase 1 study were given to expanded Philadelphia chromosome-positive B-ALL patients with remission. The 5×10\^6 cells/kg of CD19+ FTCs was the optimal biological dose determined in phase I. Therefore, CD19+ FTCs at 5×10\^6 cells/kg were infused two hours after the infusion of ssCART-19 cells on day 1 and at the same dose alone on day 8 of the second to fourth cycle, while ssCART-19 was infused at the dose of 5×10\^6/kg on days 1 to 3 of the first cycle and on day 1 of the second to fourth cycle. The Bayesian optimal design was applied to perform the futility assessment at the specified interim analyses. Thirty-eight evaluable subjects were recruited, and all the patients received at least two cycles of ssCART-19 consolidation.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

15 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-07-10

Primary Completion

2025-07-20

Completion

2040-07-20

Countries

• China

Study Locations