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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FTCs: High dose (Phase 1) | Experimental |
| |
| FTCs: Medium dose (Phase 1) | Experimental |
| |
| FTCs: Low dose (Phase 1) | Experimental |
| |
| FTCs: High dose (Phase 2) | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 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 ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months) |
| Phase 2 Molecular response after CD19 CAR-T consolidation therapy combined with CD19+ feeding T 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 each cycle of ssCART-19 consolidation termination (each cycle is 3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 Molecular response after CD19 CAR-T consolidation therapy combined with CD19+ feeding T 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 each cycle of ssCART-19 consolidation termination (each cycle is 3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 exploratory endpoints | Assessment of persistence of CD19+ FTCs, and expansion and persistence of ssCART-19 cells in the peripheral blood | 3 months after ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months) |
| Phase 1 exploratory endpoints |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affliated Hospital of Soochow University | Suzhou | Jiangsu | 215006 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36897251 | Derived | 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. |
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Baseline characteristics of patients, outcomes
One year after the study termination
Clinical researchers worldwide can access the IPD and supporting information after author authorization. They can get IPD details by visiting the ResMan system.
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| ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion | 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. |
|
| ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion | 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. |
|
| ssCART-19 cells combined with CD19+ feeding T cells (FTCs) infusion | 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-eight evaluable subjects were recruited, and all the patients received at least two cycles of ssCART-19 consolidation. |
|
| Phase 1 The range of biologically active doses and optimal biological doses of CD19+ feeding T cells. |
The range of biologically active doses and optimal biological doses of CD19+ feeding T cells will be determined. |
| 6 months after ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months) |
| 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 |
| 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 |
| 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 ssCART-19 consolidation termination (the specific date depending how many cycles the participants received; each cycle is 3 months) |
| 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 |
| 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 |
Evaluate cytokine/chemokine induction in the blood of subjects after infusion of CD19+ FTCs and CD19 CAR-T cells |
| Two weeks during each cycle of ssCART-19 (CAR-T1-4; each cycle is 3 months) |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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