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Leukemia, Acute LymphoblasticPhase 1/2CARTHEDRALLNCT06101381

CD19-directed CAR-T Cell Therapy for R/R Acute Leukemia and Lymphoma

A Phase 1/2 study testing CART-19 in people with Leukemia, Acute Lymphoblastic and Lymphoma, Non-Hodgkin, run by University of Sao Paulo at 5 sites in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 3 to 70 years
What is being tested?
CART-19
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
5 sitesBrazil
Study dates
21 Mar 2024to Dec 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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);
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  • 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
  • Failure to mobilize and/or collect hematopoietic progenitor cells (HPC), as defined by the investigator.
  • Measurable disease, defined as:
  • Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
  • Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long axis, regardless of the length of the short axis.
  • Adequate organ function:
  • Renal function defined as:
  • estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m2
  • Hepatic function defined as:
  • Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 × ULN; and
  • Total bilirubin ≤ 1.5 × ULN, except for patients with Gilbert syndrome.
  • Hematologic Function (regardless of transfusions for 14 days) defined as:
  • Absolute neutrophil count (ANC) >500/uL
  • Platelets ≥ 50,000/uL
  • Hemoglobin >7.0 g/dl
  • In women of childbearing potential, willingness to use effective means of birth control for 1 year after CAR-T cell infusion.
  • In male participants, willingness to use a barrier birth control method for 1 year after CAR-T cell infusion
  • Able to comply with inpatient treatment, outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
  • For Acute Lymphoblastic Leukemia (B-ALL):
  • Provision of signed Informed Consent form;
  • Age ≥ 3 and < 25 years;
  • Performance status < 2, according to the Eastern Cooperative Oncology Group for patients ≥ 16 years old, or ≥ 50%, according to the Lansky performance status for patients younger than 16 years old;
  • Relapsed or refractory CD19 positive B-ALL, with documentation of CD19 disease expression within 3 months of screening visit.
  • Relapsed or refractory disease as defined below;
  • Failure to obtain hematologic complete remission (bone marrow with < 5% lymphoblasts by morphologic assessment) after 2 distinct chemotherapy lines; or
  • Relapsed or refractoriness after at least 1 previous chemotherapy regimen and ineligibility for allogeneic hematopoietic progenitor cell transplantation (HSCT) due to lack of available donor (including alternative donors), comorbidity, have previously undergone or refused HSCT; or
  • Relapsed disease ≥ 6 months after HSCT; or
  • Relapsed or refractoriness after ≥ TKi for Philadelphia-positive B-ALL.
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment within 30 days from screening
  • Adequate organ function:
  • Renal function defined as:
  • Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m2
  • Hepatic function defined as:
  • Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 5 × ULN; and
  • Total bilirubin ≤ 2 × ULN, except for patients with Gilbert syndrome.
  • In women of childbearing potential, willingness to use effective means of birth control for 1 year after CAR-T cell infusion.
  • In male participants, willingness to use a barrier birth control method for 1 year after CAR-T cell infusion
  • Able to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation. duration of the parent study and the long-term follow-up observational study

Who cannot join

  • 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.
Show all 75Show fewer
  • 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;
  • History of previous tuberculosis;
  • Positive Chagas disease serology;
  • Hepatitis B or hepatitis C testing indicating active/ongoing infection, as defined as:
  • HBV: Patients with positive HBsAg are excluded. Patients with positive anti-HBc and negative HBsAg require hepatitis B PCR evaluation before randomization. Patients who are hepatitis B PCR-positive will be excluded.
  • HCV: Patients with positive hepatitis C antibody may be enrolled with a negative result for hepatitis C RNA before study inclusion. Patients who are hepatitis C RNA-positive will be excluded.
  • History of a symptomatic CNS disease (or which required treatment within the past year), such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease;
  • Significant cardiovascular disease defined as ≥ grade 3 New York Heart Association functional classification system of heart failure, history of myocardial infarction, uncontrolled or symptomatic arrhythmias, or unstable angina within the past 6 months before the screening;
  • Chronic lung disease, with hypoxemia (Oxygen saturation measured by pulse oximetry > 93% on room air), or uncontrolled within 4 weeks before the screening visit
  • History of an autoimmune disease (including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis) with end-organ damage or requiring systemic immunosuppression/systemic disease-modifying agents in the 2 years preceding the screening visit;
  • Participants with hypothyroidism receiving a stable dose of thyroid replacement hormone may be eligible.
  • Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • History of deep vein thrombosis or pulmonary embolism within 6 months before the screening visit, or need to use systemic anticoagulation at the time of screening for any other reason;
  • Major surgery within 4 weeks of the screening visit;
  • History or suspicion of hemophagocytic lymphohistiocytosis (HLH);
  • Vaccination with a live or attenuated virus vaccine within one month before the screening visit;
  • Patients with known hypersensitivity, including anaphylaxis, to any component of the investigational treatment;
  • Pregnancy, lactation, or plan to get pregnant during the study or within 12 months after CAR-T cell infusion;
  • In women of childbearing potential a negative serologic pregnancy test must be obtained 7 days before CAR-T cell infusion;
  • Women of childbearing potential, and all male participants, must be willing to observe barrier and highly effective birth control methods (outlined in the study protocol) for 12 months following CAR-T cell infusion;
  • Presence of any other medical condition that in the investigator's opinion may interfere with the safety or effectiveness evaluation of the study;
  • Life expectancy less than 12 weeks, by investigator assessment.
  • For Acute Lymphoblastic Leukemia (B-ALL)::
  • 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;
  • Isolated extramedullary disease;
  • Active central nervous system (CNS) involvement by disease (CNS-3 according to NCCN guideline), detected by cytology/immunophenotyping of cerebrospinal fluid (CSF) within 30 days from screening visit.
  • Patients with CNS-1 and CNS-2 within 30 days from screening visit may be enrolled;
  • Burkitt's Leukemia/Lymphoma
  • Active acute or chronic graft-versus-host disease (GvHD), or controlled with immunosuppressants in the previous 12 weeks before the screening visit;
  • Failure to obtain hematologic complete remission (bone marrow with < 5% lymphoblasts by morphologic assessment) after an anti-CD19 antibody-containing treatment (e.g. Blinatumomab);
  • History of previous CAR-T therapy;
  • History of previous solid organ transplantation;
  • 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;
  • History of previous tuberculosis;
  • Positive Chagas' disease serology;
  • Hepatitis B or hepatitis C testing indicating active/ongoing infection, as defined as:
  • HBV: Patients with positive HBsAg are excluded. Patients with positive anti-HBc and negative HBsAg require hepatitis B PCR evaluation before randomization. Patients who are hepatitis B PCR-positive will be excluded.
  • HCV: Patients with positive hepatitis C antibody may be enrolled with a negative result for hepatitis C RNA before study inclusion. Patients who are hepatitis C RNA-positive will be excluded.
  • History of a symptomatic CNS disease (or which required treatment within the past year), such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease;
  • Significant cardiovascular disease defined as ≥ grade 3 New York Heart Association functional classification system of heart failure, history of myocardial infarction, uncontrolled or symptomatic arrhythmias, or unstable angina within the past 6 months before the screening;
  • Chronic lung disease, with hypoxemia (Oxygen saturation measured by pulse oximetry > 93% on room air), or uncontrolled within 4 weeks before the screening visit
  • History of an autoimmune disease (including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis) with end-organ damage or requiring systemic immunosuppression/systemic disease-modifying agents in the 2 years preceding the screening visit;
  • Participants with hypothyroidism receiving a stable dose of thyroid replacement hormone may be eligible.
  • Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • History of deep vein thrombosis or pulmonary embolism within 6 months before the screening visit, or need to use systemic anticoagulation at the time of screening for any other reason;
  • Major surgery within 4 weeks of the screening visit;
  • History or suspicion of hemophagocytic lymphohistiocytosis (HLH);
  • Vaccination with a live or attenuated virus vaccine within one month before the screening visit;
  • Patients with known hypersensitivity, including anaphylaxis, to any component of the investigational treatment;
  • Pregnancy, lactation, or plan to get pregnant during the study or within 12 months after CAR-T cell infusion;
  • In women of childbearing potential a negative serologic pregnancy test must be obtained 7 days before CAR-T cell infusion;
  • Women of childbearing potential, and all male participants, must be willing to observe barrier and highly effective birth control methods (outlined in the study protocol) for 12 months following CAR-T cell infusion;
  • Presence of any other medical condition that in the investigator's opinion may interfere with the safety or effectiveness evaluation of the study;
  • Life expectancy less than 12 weeks, by investigator assessment.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Diego V Cle, MD, PhD, MBA contact

+551621019300

terapia@hemocentro.fmrp.usp.br

5 sites in 1 country

Brazil5 sites, 5 recruiting

  • Hospital de Clínicas da UNICAMP

    Campinas, São Paulo, 13083-888

    Carmino Souza, +55 19 35212121, carmino@unicamp.br

    Recruiting

  • Ribeirao Preto School of Medicine, University of Sao Paulo

    Ribeirão Preto, São Paulo, 14048-900

    Diego V Cle, MD, PhD, MBA, +551621019300, terapia@hemocentro.fmrp.usp.br

    Camila D Donadel, MS, +551621019300, terapia@hemocentro.fmrp.usp.br

    Recruiting

  • Hospital Sírio-Libanês

    São Paulo, São Paulo, 01308-050

    Yana Novis Zogbi, +55 11 33940200, yana.novis@hsl.org.br

    Recruiting

  • Hospital das Clinicas de São Paulo

    São Paulo, São Paulo, 05403-010

    Vanderson Rocha, +55 11 26610000, vanderson.rocha@hc.fm.usp.br

    Recruiting

  • A Beneficência Portuguesa de São Paulo

    São Paulo, São Paulo

    Phillip Scheinberg, +55 11 35051000, scheinbp@bp.org.br

    Recruiting

Other trials in Brazil

About this study

Official title: CD19-directed CAR-T Cell Therapy for Refractory or Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma: a Multicenter Phase I/II Trial.

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.

Read the detailed description

Eighty-one patients with refractory/relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) or non-Hodgkin lymphoma (B-NHL) will be included in this multicentric, phase I/II clinical trial to evaluate the safety and efficacy of a novel academic CD19-directed CAR-T cell developed in Brazil.

After the inclusion of the patient, lymphocyte apheresis will be performed for lymphocyte collection, followed by activation, transduction with a lentiviral vector, and expansion of produced CAR-T cells.

The patient will be hospitalized and receive lymphodepleting chemotherapy started five days before CAR-T cells infusion, with cyclophosphamide (300 mg/m2/day) and fludarabine (30 mg/m2/day) for three days. On Day 0, CAR-T cells will be intravenously administered over 20-30 minutes. The optimal CAR-T cell dose will be 1,7 to 5,4 x106 cells/kg, for ALL patients, and 0,6 to 6,0 x 108 cells (total dose) for NHL patients, but any dose higher than 0,2 x 106 cells/kg (for patients < 50 Kg) or 0,14 x 106 cells/kg and 0,1 x 108 cells (total dose) (for patients ≥ 50Kg), and lower than the maximal 2,6 x 108 cells (total dose) will be infused, depending on the obtained cellular product. During and after infusion, the patient will be monitored for signs and symptoms of toxicity and will remain hospitalized for at least two weeks. All patients will receive anti-viral and anti-pneumocystis prophylaxis. They will be monitored to evaluate treatment efficacy, and acute and late toxicities for five years after infusion.

Being tested
CART-19
Keywords
Cell therapy, Chimeric antigen receptor T cell, CAR-T cell, CD19, Lymphoma, Acute Leukemia
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

Study groups in NCT06101381
Study groupRoleWhat they receive
CD19-directed CAR-T cellExperimentalAfter lymphodepletion, a single intravenous infusion of an academic, locally produced, autologous CD19-directed CAR-T cells will be administered.
Receives: Biological: CART-19

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: From week 5 to week 52

Secondary outcomes (4)

  1. Efficacy: Overall Response Rate (ORR)

    The combined number of participants achieving Complete Response (CR) or Partial Response (PR) as the best response at day 30 and day 90 after CAR-T cell infusion, determined by the investigators, following Lugano criteria in non-Hodgkin lymphomas; or the combined number of participants achieving Complete Remission (CR) or Complete Remission with Incomplete Hematologic Recovery (CRi) as the best response at day 30 and day 90 after CAR-T cell infusion, determined by the investigators, in Acute Lymphoblastic Leukemia.

    Measured: Day 30 and day 90 after CAR-T cell infusion

  2. Efficacy: Event Free Survival (EFS)

    The time between patient's inclusion and relapse, disease progression, or death of any cause.

    Measured: From patient's inclusion until 5 years

  3. Efficacy: Relapse Free Survival (RFS)

    The duration of response, defined as the time from the first complete or partial response to the date of first documentation of relapse, disease progression, or death of any cause.

    Measured: From patient's inclusion until 5 years

  4. Efficacy: Overall Survival (EFS)

    The number of participants surviving since patient's inclusion until 5 years

    Measured: From patient's inclusion until 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2023
  2. Study start21 Mar 2024
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
81 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06101381
Sponsor's protocol ID
HEMO-02-CART
Acronym
CARTHEDRALL
Status last verified
Dec 2024
First submitted
4 Oct 2023
Last updated
9 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CART-19 in people with Leukemia, Acute Lymphoblastic and Lymphoma, Non-Hodgkin, run by University of Sao Paulo at 5 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 52 inclusion and 75 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Diego V Cle, MD, PhD, MBA (+551621019300, terapia@hemocentro.fmrp.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety: Number of participants who experience early adverse events. (time frame: From patient's inclusion until 30 days after CAR-T cell infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06101381.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.

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