Übersicht

Eignung

Details zum Design

Arme & Interventionen

Ergebnismessungen

Studienzentren

Quelle: NCT03984968

Rekrutiert

CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia

Interventionsstudie

Phase 1/2

The First Affliated Hospital of Soochow University

Sponsor: The First Affiliated Hospital of Soochow University

Zuletzt aktualisiert: 5. Juni 2025
Hinweis - Die Informationen stammen aus öffentlichen Registern und spiegeln möglicherweise nicht die Echtzeitänderungen am lokalen Studienzentrum wider.

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.

Behandlungskategorie

Zelltherapie

Erforderliche Mutationen

BCRABL1, CD19

Studie gestartet

10. Juli 2017

Zuletzt vom Sponsor aktualisiert

5. Juni 2025

Voraussichtlicher Abschluss

24. Januar 2025

Studienkontakt

Name:Sheng-Li Xue, M.D.

E-Mail:slxue@suda.edu.cn

Telefon:+86 512 67781139

Eignung

Einschlusskriterien

* 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

Ausschlusskriterien

* 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

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Design-Details

ZuteilungNon-Randomized

InterventionsmodellSequential Assignment

MaskierungNone (Open Label)

Anzahl der Teilnehmer34

Arme & Interventionen

Arme

Interventionen

Typ: Experimental

Beschreibung:

Interventionen:

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

Ergebnismessungen

Primäre Ergebnismessungen

Phase 1 Incidence of adverse events (AEs) and abnormal laboratory test results6 months after ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months)

AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).

Phase 2 Molecular response after CD19 CAR-T consolidation therapy combined with CD19+ feeding T cells3 months after each cycle of ssCART-19 consolidation termination (each cycle is 3 months)

Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.

Sekundäre Ergebnismessungen

Phase 1 Overall survial (OS)2 years

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.

Phase 1 Relapse free survival（RFS）2 years

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.

Phase 2 Overall survial (OS)2 years

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.

Phase 2 Relapse free survival（RFS）2 years

Phase 1 Molecular response after CD19 CAR-T consolidation therapy combined with CD19+ feeding T cells.3 months after each cycle of ssCART-19 consolidation termination (each cycle is 3 months)

Complete molecular response (CMR) was defined as the absence of a detectable BCR-ABL1 transcript with a sensitivity of 0.01%.

Phase 1 The range of biologically active doses and optimal biological doses of CD19+ feeding T cells.6 months after ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months)

The range of biologically active doses and optimal biological doses of CD19+ feeding T cells will be determined.

Phase 2 Incidence of adverse events (AEs) and abnormal laboratory test results6 months after ssCART-19 consolidation termination (the specific date depending how many cycles the participants received; each cycle is 3 months)

AEs will be assessed according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0).

Phase 1 exploratory endpoints3 months after ssCART-19 consolidation termination (CAR-T4; each cycle is 3 months)

Assessment of persistence of CD19+ FTCs, and expansion and persistence of ssCART-19 cells in the peripheral blood

Phase 1 exploratory endpointsTwo weeks during each cycle of ssCART-19 (CAR-T1-4; each cycle is 3 months)

Evaluate cytokine/chemokine induction in the blood of subjects after infusion of CD19+ FTCs and CD19 CAR-T cells

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Studienzentren

Diese Studie hat 1 Studienzentrum

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, CN

Name:Sheng-Li Xue, M.D.

Rekrutierend

Suzhou, Jiangsu, 215006 CN

The First Affliated Hospital of Soochow University

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