ThisCART19A Bridging to alloHSCT for R/R B-ALL

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

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).

Study Overview

• Status: Recruiting
• Conditions: CAR; Refractory Acute Lymphoblastic Leukemia; Relapsed Adult ALL
• Intervention / Treatment: Drug: Treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jia Chen, M.D., Ph.D.; Phone Number: +86-512-67781856; Email: drchenjia@163.com
• Study Contact Backup: Name: Jun Li, Ph.D.; Phone Number: +86-18662604088; Email: jli@ctigen.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure.
2. No gender limitation, 14 years ≤ age ≤ 65 years.
3. Intention to HSCT therapy.
4. 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.
5. Life expectancy ≥ 8 weeks at the time of enrollment.
6. Eastern Cooperative Oncology Group performance status score of 0 or 1.

7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function:

   1. Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator.
   2. Creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula;
   3. 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.)
   4. Oxygen saturation (SaO2) ≥ 92% on room air.
   5. Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
8. CD19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening.

Exclusion Criteria:

1. Allergic to preconditioning measures.
2. History of allogeneic HSCT.
3. 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.)
4. Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.)
5. Pulmonary embolism within 3 months prior to enrollment.
6. Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment.
7. Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging;
8. 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.)
9. 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.)
10. 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.
11. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Fundamenta Therapeutics, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): November 30, 2025
• Study Completion (Anticipated): November 30, 2025

Study Registration Dates

• First Submitted: December 27, 2022
• First Submitted That Met QC Criteria: December 27, 2022
• First Posted (Estimate): January 11, 2023

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Universal CAR-T; allogeneic HCT
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: SZ4602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No