NCT06101381

Brief Summary

The goal of this prospective, multicentric, single-arm, phase I/II clinical trial is to evaluate the safety and efficacy of a novel CD19-directed CAR-T cell locally produced in an academic institution in Brazil in patients with refractory or relapsed acute lymphoblastic leukemia or non-Hodgkin lymphoma. Participants will receive a single intravenous infusion of an autologous academic anti-CD19 CAR-T cell and will be followed for 5 years.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
81

participants targeted

Target at P75+ for phase_1

Timeline
31mo left

Started Mar 2024

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress45%
Mar 2024Dec 2028

First Submitted

Initial submission to the registry

October 4, 2023

Completed
22 days until next milestone

First Posted

Study publicly available on registry

October 26, 2023

Completed
5 months until next milestone

Study Start

First participant enrolled

March 21, 2024

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

December 9, 2024

Status Verified

December 1, 2024

Enrollment Period

4.7 years

First QC Date

October 4, 2023

Last Update Submit

December 4, 2024

Conditions

Leukemia, Acute LymphoblasticLymphoma, Non-Hodgkin

Keywords

Cell therapyChimeric antigen receptor T cellCAR-T cellCD19LymphomaAcute Leukemia

Outcome Measures

Primary Outcomes (2)

  • Safety: Number of participants who experience early adverse events.

    To evaluate the occurrence of early adverse events related to the study treatment, from inclusion until 30 days after CAR-T cell infusion.

    From patient's inclusion until 30 days after CAR-T cell infusion

  • Safety: Number of participants who experience late adverse events.

    To evaluate the occurrence of early adverse events related to the study treatment, from week 5 to week 52.

    From week 5 to week 52

Secondary Outcomes (4)

  • Efficacy: Overall Response Rate (ORR)

    Day 30 and day 90 after CAR-T cell infusion

  • Efficacy: Event Free Survival (EFS)

    From patient's inclusion until 5 years

  • Efficacy: Relapse Free Survival (RFS)

    From patient's inclusion until 5 years

  • Efficacy: Overall Survival (EFS)

    From patient's inclusion until 5 years

Other Outcomes (2)

  • Exploratory: Number of patientes with CAR-T cell persistence over the time

    From CAR-T cell infusion until 5 years

  • Exploratory: Replication-competent lentivirus (RCL)

    From CAR-T cell infusion until 5 years

Study Arms (1)

CD19-directed CAR-T cell

EXPERIMENTAL

After lymphodepletion, a single intravenous infusion of an academic, locally produced, autologous CD19-directed CAR-T cells will be administered.

Biological: CART-19

Interventions

CART-19BIOLOGICAL

The academic CART-19 consists of autologous T lymphocytes transduced with a lentiviral vector to express a second-generation chimeric antigen receptor with a single chain variable fragment (scFv) targeting the CD19 antigen conjugated with 4-1BB co-stimulatory and CD3z signaling domains.

CD19-directed CAR-T cell

Eligibility Criteria

Age3 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • For non-Hodgkin Lymphomas (B-NHL):
  • Provision of signed Informed Consent form;
  • Age between 18 and 70 years;
  • Performance status according to the Eastern Cooperative Oncology Group \< 2;
  • Relapsed or refractory B-NHL of the following types (confirmed by biopsy):
  • Diffuse large B-cell lymphoma (DLBCL, NOS);
  • High-grade B-cell lymphoma (HGBCL);
  • Diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL-2 rearrangement;
  • Follicular lymphoma (FL) grade 3B; or
  • Transformed follicular lymphoma (tFL)
  • Refractory or relapsed to two or more lines of systemic therapy, with at least one scheme containing an anti-CD20 monoclonal antibody and anthracycline, as defined below:
  • Refractoriness: partial response (PR), stable disease (SD), or progressive disease (PD) as the best response to the last treatment, assessed by PET-CT, according to the Lugano criteria and confirmed by a new biopsy.
  • Relapsed disease: disease reappearance after obtaining a complete response to the last treatment, assessed by PET-CT, according to the Lugano criteria and confirmed by a new biopsy.
  • Have performed, or be ineligible for, autologous hematopoietic progenitor cell transplantation (ASCT). Ineligibility is defined by:
  • Lack of at least partial response after salvage chemotherapy; or
  • +37 more criteria

You may not qualify if:

  • For non-Hodgkin Lymphomas (B-NHL):
  • Previous or concurrent cancer distinct from B-NHL within 2 years before screening, except for the following:
  • Curatively treated nonmelanomatous skin cancer;
  • Curatively treated cervical carcinoma in situ;
  • Localized breast cancer treated with curative intent with no evidence of active disease; or
  • Localized prostate cancer undergoing active surveillance or anti-androgenic therapy, without evidence of metastatic disease.
  • Syndromes and/or genetic diseases with impact on the hematopoietic system, including Down's syndrome, Fanconi anemia, telomeropathies, Li Fraumeni, Blackfan-Diamond anemia, or congenital immunodeficiencies;
  • History of previous CAR-T therapy;
  • History of previous solid organ transplantation;
  • Active central nervous system (CNS) involvement by disease, detected by image or cytology/immunophenotyping of cerebrospinal fluid (CSF);
  • Primary central nervous system lymphoma (PCNSL);
  • Primary mediastinal large B cell lymphoma (PMBCL);
  • Evidence of uncontrolled systemic infection (viral, bacterial, or fungal) which requires IV antibiotics, within 2 weeks before the screening visit;
  • Known HIV infection;
  • Known HTLV I and II infection;
  • +58 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Hospital de Clínicas da UNICAMP

Campinas, São Paulo, 13083-888, Brazil

RECRUITING

Ribeirao Preto School of Medicine, University of Sao Paulo

Ribeirão Preto, São Paulo, 14048-900, Brazil

RECRUITING

Hospital Sírio-Libanês

São Paulo, São Paulo, 01308-050, Brazil

RECRUITING

Hospital das Clinicas de São Paulo

São Paulo, São Paulo, 05403-010, Brazil

RECRUITING

A Beneficência Portuguesa de São Paulo

São Paulo, São Paulo, Brazil

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Non-HodgkinLymphoma

Interventions

CTL019 chimeric antigen receptor

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Diego V Cle, MD, PhD, MBA

    Ribeirao Preto School of Medicine, University of Sao Paulo

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego V Cle, MD, PhD, MBA

CONTACT

+551621019300terapia@hemocentro.fmrp.usp.br

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Coordinator

Study Record Dates

First Submitted

October 4, 2023

First Posted

October 26, 2023

Study Start

March 21, 2024

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

December 9, 2024

Record last verified: 2024-12

Data Sharing

IPD Sharing
Will not share

Locations

BR(5)