U69-CART-Cells For R/R T-ALL
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age15-75
SponsorThe First Affiliated Hospital of Soochow University
About this trial
Overall Introduction This single-arm, open-label clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of CXCR4-enabled CCR9 chimeric antigen receptor T-cell injection (CXCR4 CCR9 CAR-T) in patients with relapsed or refractory T-lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL). Additionally, the study seeks to preliminarily assess the efficacy of CXCR4 CCR9 CAR-T cells and explore the appropriate dosage and administration schedule for subsequent Phase II clinical trials. A dose escalation study following the 3+3 design was implemented across three dose cohorts, with each cohort planned to enroll 3 to 6 patients, totaling 9 to 18 participants. Following cell infusion, subjects underwent safety and efficacy follow-up, which continued until 2 years post-infusion, subject withdrawal, or study termination-whichever occurred first. For subjects with available follow-up information after study completion or early termination, long-term follow-up-including long-term safety monitoring-was conducted for up to 15 years.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Informed Consent: Voluntary provision of written informed consent and anticipated ability to complete all required study procedures and follow-up assessments.
Age: ≥15 and ≤75 years of age at the time of signing the informed consent form.For minors (age ≤ 18 years), informed consent must be provided by a legal guardian; minors with capacity to sign should co-sign the consent form alongside their guardian.
Diagnosis and Disease Status: Histologically or cytologically confirmed diagnosis of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) according to the 2022 WHO Classification of Haematolymphoid Tumours, for which standard curative treatments are no longer effective.
Biomarker: Confirmed CCR9 positivity on tumor cells via flow cytometry of bone marrow samples and/or via immunohistochemistry of extramedullary lesion biopsies at screening.
Disqualifiers
Diagnosis of any other malignancy within 3 years prior to screening, except for those who have completed curative therapy and achieved over 3 years of disease-free survival with a low risk of recurrence as determined by the investigator (e.g., carcinoma in situ of the lung, basal cell carcinoma of the skin).
History or presence of central nervous system (CNS) disorders unrelated to the disease under study at screening or previously, such as seizure, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS.
Prior receipt of cell therapies targeting CCR9, including but not limited to CAR-T or CAR-γδT cells.
Significant or active parenchymal CNS or cranial nerve lesions where, in the investigator's judgment, the risks outweigh the benefits.
Trial design
Design model
Sequential
Treatments tested in this trial
CXCR4 CCR9 CAR-T
DrugCXCR4-enabled CCR9 chimeric antigen receptor T-cell injection solution
Treatment groups
12 Participants
are divided into 3 treatment groupsGroup A: Low-dose groupExperimental treatment 1 intervention
Group B: Medium dose groupExperimental treatment 1 intervention
Group C: High dose groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-limiting toxicity (DLT)
DLT refers to any of the following conditions occurring within 28 days after cell reinfusion that are related to cell infusion: ① Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) not caused by the underlying disease and taking more than 30 days to resolve to ≤ Grade 2. ② Non-hematologic DLT: Any toxicity ≥ Grade 4 that is possibly related to CAR-T therapy, or Grade 3 toxicity that requires ≥7 days to resolve to ≤ Grade 2 or to return to baseline.
Time frame
Within 28 days after CXCR4 CCR9 CAR-T cell infusion2
Adverse Event (AE）
Record the types, occurrence frequency and severity of adverse events (AEs) related to CAR-T, with specific definitions determined according to CTCAE v5.0.The CRS and ICANS ratings do not use CTCAE but adopt the evaluation criteria in the ASTCT standards.
Time frame
2 years3
The Recommended Phase II Dose（RP2D）
The dose recommended for use in phase 2 studies on the basis of dose limiting toxicities observed in phase 1 studies.
Time frame
Within 28 days after CXCR4 CCR9 CAR-T cell infusionSecondary outcomes
1
Objective Response Rate (ORR)
Defined as the proportion of subjects achieving an objective response (complete or partial response). All subjects not meeting the objective response criteria as of the data cutoff date will be considered non-responders. ①For T-ALL patients: Treatment response is defined as the achievement of either Complete Remission (CR) or Complete Remission with Incomplete Hematologic Recovery (CRi); ②For T-LBL patients: Treatment response is defined as the achievement of either Complete Response (CR) or Partial Response (PR);
Time frame
28 days and within 3 months after infusion of CXCR4 CCR9 CAR-T cells2
MRD-negative rate (for T-ALL)
The proportion of T-ALL patients with negative MRD in the bone marrow when the therapeutic effect reaches remission. T-ALL patients have residual leukemia cells in the bone marrow detected by flow cytometry below 10-⁴ and/or negative qualitative or quantitative detection of bone marrow fusion genes (if any).
Time frame
28 days and within 3 months after infusion of CXCR4 CCR9 CAR-T cells3
Duration of Response (DOR)
It refers to the period from the time when the subject first achieves remission to the time of disease progression or death due to the disease. Subjects who have not experienced disease progression or death by the time of the final data collection will be censored at the time of their last valid tumor assessment. Common reasons for censoring include, but are not limited to: * Loss to follow-up; ②Withdrawal from the study; ③Initiation of a new anticancer therapy.
Time frame
2 years4
Progression-Free Survival (PFS)
Defined as the time from the date of cell infusion to the date of first documented disease progression or death from any cause, whichever occurs first. Subjects who have not experienced disease progression or death by the data cutoff date will be censored at the time of their last tumor assessment.
Time frame
2 yearsSponsors and contacts
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Source ClinicalTrials.gov