CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

NCT ID: NCT03984968

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-10
• Study Completion Date: 2040-01-24

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FTCs: High dose (Phase 1)

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

FTCs: Medium dose (Phase 1)

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

FTCs: Low dose (Phase 1)

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

FTCs: High dose (Phase 2)

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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-four evaluable subjects were recruited, and all the patients received at least two cycles of ssCART-19 consolidation.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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-four evaluable subjects were recruited, and all the patients received at least two cycles of ssCART-19 consolidation.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 15-65 years of age at the time of signing informed consent
• Diagnosed as de novo Philadelphia chromosome-positive CD19+ B-ALL
• Karnofsky performance status ≥ 60 or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Unable to find a suitable donor or for other reasons to undergo allogeneic hematopoietic stem cell transplantation during the study
• Ability and willingness to adhere to the study visit schedule and all protocol requirements
• Voluntarily sign informed consent forms

Exclusion Criteria

• Unable to tolerate any kind of TKIs (including the first- and second-generation tyrosine kinase inhibitors) for a long period.
• Subjects who have positive mutation(s) of the ABL kinase domain and require the third-generation tyrosine kinase inhibitors for long-term therapies.
• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) and direct bilirubin > 1.5 × ULN
• Inadequate renal function defined by serum creatinine > 1.6 mg/dL
• International ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN
• Left ventricular ejection fraction < 50%
• Ongoing treatment with chronic immunosuppressants
• Significant comorbid conditions or diseases which, in the judgment of the investigator, would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
• Known human immunodeficiency virus (HIV) positivity
• Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
• Subjects with second malignancies in addition to ALL
• Pregnant or lactating women, or subjects refusing to take effective contraception measures
• Other contraindications that are considered inappropriate to participate in this trial

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Sheng-Li Xue, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sheng-Li Xue, M.D.

Role: CONTACT

slxue@suda.edu.cn

+86 512 67781139

Facility Contacts

Sheng-Li Xue, M.D.

Role: primary

slxue@suda.edu.cn

+86 512 6778 1139

References

Chen LY, Gong WJ, Li MH, Zhou HX, Xu MZ, Qian CS, Kang LQ, Xu N, Yu Z, Qiao M, Zhang TT, Zhang L, Tian ZL, Sun AN, Yu L, Wu DP, Xue SL. Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia. Blood Adv. 2023 Sep 12;7(17):4913-4925. doi: 10.1182/bloodadvances.2022009072.

Reference Type: DERIVED

PMID: 36897251 (View on PubMed)

Other Identifiers

SZCART01

Identifier Type: -

Identifier Source: org_study_id