Inaticabtagene Autoleucel (Inati-cel; CNCT19) Treatment for Newly Diagnosed B-cell ALL Patients in CR1

NCT06777264 | Not Yet Recruiting Phase 2

• 1 other identifier: [2024]TXB ethic review NO.023
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This investigator-initiated, prospective, single-arm, open-label, single-center phase II study aims to evaluate the long-term survival benefit and safety of a commercial CD19 CAR-T product in newly diagnosed Philadelphia chromosome-positive or negative (Ph-positive or Ph-negative) B-cell ALL patients who achieve CR1 after induction chemotherapy. A total of 20 patients will be enrolled in the study. The primary endpoints include disease-free survival (DFS) and overall survival (OS) rates after a median follow-up of 2 years, minimal residual disease (MRD) negativity rate, and the proportion of patients undergoing subsequent hematopoietic stem cell transplantation (HSCT). The frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after infusion will also be recorded.

Conditions

Acute Lymphoblastic Leukemia; B Cell ALL

Keywords

Chimeric Antigen Receptor T (CAR-T)Cell; Acute Lymphoblastic Leukemia; B-ALL; Inaticabtagene Autoleucel

Outcome Measures

Primary Outcomes (4)

• 2-year DFS rate (2yDFSR)

  The proportion of patients who remain free from bone marrow disease relapse or death from any cause, assessed after a median follow-up of 2 years

  Up to 2 years

• 2-year OS rate (2yDFSR)

  The proportion of patients who remain alive after a median follow-up of 2 years

  Up to 2 years

• DFS

  The time from Inati-cel infusion to morphological relapse of B-ALL in the bone marrow, or death from any cause (whichever occurs first).

  Up to 2 years

• OS

  The time from Inati-cel infusion to death from any cause

  Till the end of the study, up to 5 years

Secondary Outcomes (5)

• Proportion of patient underwent subsequent hematopoieticstem cell transplantation

  Till the end of the study, up to 5 years

• MRD negativity rate

  6 months

• Maximum observed concentration(Cmax)

  6 months

• Time of Cmax (Tmax)

  6 months

• Partial area under the concentration-time curve (from time zero to 28days after dosing , AUC 0-28 day)

  6 months

Study Arms (1)

Biological: Inaticabtagene autoleucel

EXPERIMENTAL

Administration of Inaticabtagene Autoleucel (CD19 CAR-T cells) in newly diagnosed B-ALL patients aged 14 to 70 years in their first complete remission (CR1).

Biological: Biological: single dose of Inaticabtagene autoleucel

Interventions

Biological: single dose of Inaticabtagene autoleucel BIOLOGICAL

Inaticabtagene autoleucel will be transfusioned intravenously at the recommended dose of 0.5×10\^8 (ranging 0.2-0.6×10\^8) viable CAR-T cells.

Also known as: Inati-cel, CNCT-19

Biological: Inaticabtagene autoleucel

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥14 years and ≤70 years at screening, with no restrictions on gender.
• ECOG performance status of 0 to 1.
• Newly diagnosed B-ALL within 12 months and achieving CR1 after standard induction chemotherapy. This includes B-ALL patients with \<5% bone marrow blasts, no blasts in peripheral blood, and no extramedullary leukemia. Diagnosis and chemotherapy regimen follow the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2021 Edition).
• At the time of B-ALL diagnosis, leukemia cells in bone marrow or peripheral blood confirmed as CD19-positive via flow cytometry.
• Adequate organ function meeting the following criteria:
• Aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN).
• Alanine aminotransferase (ALT) ≤3× ULN.
• Total bilirubin ≤2× ULN (for patients with Gilbert's syndrome, total bilirubin ≤3.0× ULN and direct bilirubin ≤1.5× ULN).
• Serum creatinine ≤1.5× ULN, or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula).
• International Normalized Ratio (INR) ≤1.5× ULN and activated partial thromboplastin time (APTT) ≤1.5× ULN.
• Minimum pulmonary reserve defined as ≤Grade 1 dyspnea and oxygen saturation \>91% on room air.
• No intent or eligibility for hematopoietic stem cell transplantation.
• Meets the leukapheresis standards of the study center, with no contraindications for apheresis.
• Women of childbearing potential must have a negative blood/urine pregnancy test during the Inati-cel screening period and before preconditioning (results within three days prior to preconditioning). All male and female patients of childbearing potential must agree to use effective contraception throughout the study and for at least two years following study treatment. A female is considered of childbearing potential if biologically capable of having children and engaging in regular sexual activity. Women are considered not of childbearing potential if they meet at least one of the following:
• History of hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.

You may not qualify if:

• Diagnosis of Burkitt lymphoma/leukemia, heterozygous or double-hit leukemia, or chronic myeloid leukemia in blast crisis.
• Presence of ≥5% blasts in the bone marrow or peripheral blood, or evidence of extramedullary leukemia before screening or preconditioning.
• Prior treatment with CAR-T cell therapy or hematopoietic stem cell transplantation (HSCT) before screening or preconditioning.
• Genetic syndromes associated with bone marrow failure, including Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other known bone marrow failure syndromes.
• Presence of any of the following conditions:
• Positive for HBsAg and/or HBeAg.
• Positive for HBe-Ab and/or HBc-Ab with HBV-DNA levels above the detectable threshold.
• Positive for HCV-Ab.
• Positive for TP-Ab.
• EBV-DNA or CMV-DNA levels above the detectable threshold.
• Positive for HIV antibodies.
• Diagnosis of other malignancies within the past 5 years, unless the tumor was curatively treated, with a follow-up period exceeding 5 years, and a low risk of recurrence as assessed by the investigator.
• Presence of any of the following cardiac conditions:
• Left ventricular ejection fraction (LVEF) ≤45%.
• Congestive heart failure classified as NYHA class III or IV.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma

Interventions

Biological Products

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Complex Mixtures

Central Study Contacts

Jie Jin

CONTACT

0571-87236898; jiej0503@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2024
• First Posted: January 15, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: January 15, 2025

Record last verified: 2024-12