ThisCART19A Bridging to alloHSCT for R/R B-ALL

Study Overview
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Brief Summary
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This is a phase 1, open-label study to assess the efficacy, safety and pharmacokinetics of ThisCART19A (Allogeneic Anti CD19 CAR-T) bridging to HSCT in patients with refractory or relapsed B cell acute lymphoblastic leukemia (r/r B-ALL).

Detailed Description
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This is a phase 1, single-center, nonrandomized, open-label, dose-escalation study to evaluate the efficacy, safety and pharmacokinetics of ThisCART19A bridging to HSCT in patients with CD19 positive r/r B-ALL and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile. Before initiating ThisCART19A infusion, subjects will be administered lymphodepletion chemotherapy composed of fludarabine、cyclophosphamide and VP-16. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of ThisCART19A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of ThisCART19A will be followed up to 2 years.

Official Title
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A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic Anti CD19 CAR-T Bridging to Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia

Conditions
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CAR, Refractory Acute Lymphoblastic Leukemia, Relapsed Adult ALL

Intervention / Treatment
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* Drug: Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily sign a documented IRB-approved ICF prior to any screening procedure. No gender limitation, 14 years ≤ age ≤ 65 years. Intention to HSCT therapy. Meeting the diagnostic criteria of relapsed or refractory B-ALL. Relapsed B-ALL: Reappearance of blasts in the blood or bone marrow (>5%) or in any extramedullary site after a CR. Refractory B-ALL: Failure to achieve CR or CRi at the end of induction therapy (General refers to a 4-week regimen or a Hyper-CVAD regimen); Subjects with Ph+ disease are eligible if they are intolerant to TKI therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs. Life expectancy ≥ 8 weeks at the time of enrollment. Eastern Cooperative Oncology Group performance status score of 0 or 1. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function: Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator. Creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula; ALT and AST ≤ 5 × ULN (the upper limit of normal), total bilirubin ≤ 2×ULN. (Subjects with Gilbert syndrome or liver involvement may be included if their total bilirubin is ≤ 3 × ULN.) Oxygen saturation (SaO2) ≥ 92% on room air. Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography. CD19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening. Exclusion Criteria: Allergic to preconditioning measures. History of allogeneic HSCT. Other malignancies apart from B-cell malignancies within 5 years prior to screening. (Subjects with cured skin squamous carcinoma, basal cell carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be enrolled.) Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.) Pulmonary embolism within 3 months prior to enrollment. Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment. Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging; Active hepatitis B virus (defined as serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Subjects with HBV-DNA < 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.) Vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (Subjects vaccinated with SARS-COV19 vaccine or inactivated, live/non-live adjuvant vaccines can be enrolled.) Female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after CAR-T cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after CAR-T cell infusion. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>In this study, allogeneic anti-CD19 CAR T cells (ThisCART19A) infusion is used as a bridge therapy to hematopoietic stem cell transplantation to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. Lymphodepletion conditioning before CAR T cell infusion consists of fludarabine, CTX and VP-16. | Drug: Treatment<br>* In this study, allogeneic anti-CD19 CAR T cells (ThisCART19A) infusion is used as a bridge therapy to hematopoietic stem cell transplantation to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. Lymphodepletion conditioning before CAR T cell infusion consists of fludarabine, CTX and VP-16.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall response rate | 4 week | 
| MRD Negativity | MRD Negativity is assessed utilizing multicolor flow cytometry to detect leukemia cells with a sensitivity of 10^ (-4). | 4 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR | Complete response | 2 year | 
| CRi | CR with incomplete hematologic recovery | 2 year | 
| CRh | CR with partial hematological recovery | 2 year | 
| BFBM | Blast-free hypoplastic or aplastic bone marrow | 2 year | 
| PR | Partial response | 2 year | 
| DOR | Duration of response | 2 year | 
| LFS | Leukemia-free survival | 2 year | 
| OS | Overall survival | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Universal CAR-T, allogeneic HCT