CD19 CAR T-Cell Therapy for R/R Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia

• ClinicalTrials.gov Identifier: NCT06027957
• Recruitment Status: Recruiting
• First Posted: September 7, 2023
• Last Update Posted: September 7, 2023
• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
• Collaborator: National Institute of Hematology and Blood Transfusion, Vietnam
• Information provided by (Responsible Party): Vinmec Research Institute of Stem Cell and Gene Technology

Study Description

Brief Summary:

• Brief Summary: Cluster of differentiation 19 (CD19) is expressed on B cells. CD19+ tumor cells in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia can be targeted using T cells expressing CD19-specific chimeric antigen receptor (CAR).
• Objective: This study aims to evaluate the safety and efficacy of single-dose anti-CD19 CAR T-cell therapy in the treatment of relapsed/refractory CD19+ non-Hodgkin lymphoma and acute lymphoblastic leukemia.
• Eligibility: People aged 1 to 60 years with relapsed/refractory CD19+ non-Hodgkin lymphoma and acute lymphoblastic leukemia.
• Design: Phase 1 clinical trial, uncontrolled, single dose of CD19 CAR T-cells.

Condition or disease	Intervention/treatment	Phase
B-Cell Non Hodgkin Lymphoma; B-Cell Acute Lymphoblastic Leukemia	Biological: anti-CD19 CAR T-cells	Phase 1

Detailed Description:

Objectives:

• Evaluate the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy.

• Evaluate the response rate after CD19 CAR T-cell infusion according to the following criteria:

  • Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion
  • Progression-free survival (PFS) after infusion of CD19 CAR T-cells
  • Event-free survival (EFS) after infusion of CD19 CAR T-cells
  • Overall survival (OS) after infusion of CD19 CAR T-cells

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Clinical Trial Evaluating the Safety and Efficacy of Point-of-care CAR-T-cell Therapy in the Treatment of Relapsed/Refractory CD19+ Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia
• Actual Study Start Date: August 2, 2023
• Estimated Primary Completion Date: July 31, 2025
• Estimated Study Completion Date: July 31, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment Regimen; Experimental: Treatment Regimen.; Leukapheresis to collect white blood cells using Spectra Optia Apheresis system.; T cells selection, transduction, and CAR T-cell manufacturing using CliniMACS Prodigy. During this process, T cells will be genetically modified to express CD19 CAR.; Lymphodepleting chemotherapy conditioning regimen for 3 days.; CAR T-cells targeting CD19 will be infused intravenously at a dose between 1 and 2x10e6 cells/kg for 15-30 minutes.; Following the T-cell infusion, patients will stay in the clinic for approximately 21-28 days to monitor toxicity.; Outpatient follow-up will take place after 1 month, 3 months, and 6 months after infusion.

Biological: anti-CD19 CAR T-cells; For Biological: CD19 CAR T-cells; Dose: 1-2.10e6 cells/kg of weight; Route: intravenous infusion For Chemotherapy Drug: Fludarabine (30 mg/m2/day) given intravenously (IV) on day -5 to -3.; Cyclophosphamide 500 mg/m2/day for NHL and 250 mg/m2/day for ALL given IV from day -5 to -3.; Mesna 500 mg/m2/day for NHL and 250 mg/m2/day for ALL, divided in three infusions: one day before the cyclophosphamide infusion, and 4 and 8 hours after.; Other Name: Chemotherapy Drug

Outcome Measures

Primary Outcome Measures :

1. Assessment of the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy [ Time Frame: 6 months ]
   The incidence of adverse events (AEs) and serious adverse events (SAEs) will be recorded and classified according to CTCAE v5 (grade 1-5). CRS and ICANs will be classified using the ASTCT criteria (grade 1-5). These parameters will be used to assess the safety of the therapy.

Secondary Outcome Measures :

1. Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion (%) [ Time Frame: Day 30 and day 90 after CAR-T infusion for B-ALL; day 90 after CAR-T infusion for NHL ]

   Patients with B-ALL will receive bone marrow biopsy assessed on day 30 and day 90 to check blast frequency and MRD. The response will be classified according to NCCN guidelines.

   Patients with NHL will be examined PET-CT or CT on day 90. The response will be classified according to Cheson guidelines.

2. Progression-free survival (PFS) (months) [ Time Frame: 6 months ]
   PFS is defined as the time from CAR T-cell infusion, until disease progression or death from any cause. Progression is defined as an increase of tumor load, the development of new lesions.
3. Event-free survival (EFS) (months) [ Time Frame: 6 months ]
   EFS is defined as time to treatment failure (including complete remission with incomplete hematologic or platelet recovery), relapse from complete remission, or death from any cause.
4. Overall survival (OS) (months) [ Time Frame: 6 months ]
   EFS is defined as time to death

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• B-cell acute lymphoblastic leukemia: refractory to two cycles of chemotherapy, relapsed after chemotherapy, or hematopoietic stem cell transplantation.
• B-cell non-Hodgkin lymphoma: refractory to two lines of chemotherapy, relapsed after chemotherapy, or hematopoietic stem cell transplantation.
• Age: From 1 to 60 years old (both males and females)

• Adequate organ functions:

  • Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60 mL/min/1.73 m2
  • ALT and AST ≤ 5 x ULN; Bilirubin ≤ 2.0 mg/dl
  • No chronic lung diseases, such as obstructive pulmonary disease or bronchial asthma, required continuous medications without respiratory failure (SpO2 oxygen saturation > 92% at room temperature).
  • No arrhythmia, no intracardiac thrombus or vascular wall, no heart failure, LVEF ≥ 45%

• Blood test:

  • Absolute neutrophil count (ANC) ≥ 1,000/mm3 (1 G/l) without filgrastim
  • Absolute lymphocyte count ≥ 100/mm3 (0.1 G/l)
  • Absolute platelet count ≥ 75,000/mm3 (75 G/l)
  • Hemoglobin ≥ 8.0 g/dl
• Positive for CD19 measured by immunohistochemistry or flow cytometry.
• Agree to participate in the study
• Agree to use safe methods of contraception for female patients.

Exclusion criteria:

• Involved central nervous system invasion at the time of screening.
• Medical history of veno-occlusive disease (VOD).
• Required acute treatment due to tumors such as intestinal obstructions, vascular compression, or respiratory failure.
• Having active hemolytic anemia.
• Diagnosed with primary immunodeficiency.
• Medical history of autoimmune neurological diseases or neuromyelitis.
• Receiving immunosuppressive medication, except for ≤ 30 mg prednisolone or equivalent at the time of CAR-T-cell transfusion.
• Having acute, progressive, or chronic graft-versus-host disease (GvHD).
• Having active infectious diseases determined by clinical, imaging, or other laboratory tests (blood culture, PCR, etc.)

• Patients who are critically ill or at risk of premature death characterized by:

  • Acute liver failure requiring dialysis
  • Heart failure requiring vasopressors
  • Systemic infection unresponsive to antibiotics
  • ECOG performance status ≥ 3 points at the time of screening
• Having other severe concomitant diseases (e.g., uncontrolled arterial hypertension, heart failure NYHA III-IV).
• Unstable angina within 3 months prior to screening.
• Any previous or concurrent malignancy was not B-cell lymphoma or B-ALL.
• Medical history of clinically relevant central nervous system disease, such as epilepsy, convulsions, paralysis, aphasia, uncontrolled cerebrovascular disease, traumatic brain injury, and Parkinson's disease.
• Intolerance to excipients from cellular products.
• Pregnant women or those who expect to be pregnant or reastfeeding.
• Other diseases or other conditions and circumstances that, according to the investigator's assessment, make it difficult to ensure compliance with study treatment.
• Participation in another clinical trial at the time of screening

Contacts and Locations

Contacts

Contact: Thanh Liem Nguyen, PhD; +84 4 3974 3556 ext 1420; v.liemnt@vinmec.com

Contact: Van T. Hoang, PhD; +84 93 644 94 81; v.vanht8@vinmec.com

Locations

Vietnam

Vinmec Research Institute of Stem Cell and Gene Technology; Recruiting

Hanoi, Vietnam, 100000

Contact: Nguyen T Liem, Prof

Sponsors and Collaborators

Vinmec Research Institute of Stem Cell and Gene Technology

National Institute of Hematology and Blood Transfusion, Vietnam

Investigators

• Principal Investigator: Thanh Liem Nguyen, PhD; Vinmec Research Institute of Stem Cell and Gene Technology

More Information

• Responsible Party: Vinmec Research Institute of Stem Cell and Gene Technology
• ClinicalTrials.gov Identifier: NCT06027957
• Other Study ID Numbers: ISC19.26
• First Posted: September 7, 2023
• Last Update Posted: September 7, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases