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Relapsed/refractory LymphomaEarly Phase 1NCT06756321

A Study of CAR T-Cells in Relapsed/Refractory Hematologic Malignancy

A Early Phase 1 study testing anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells, Fludarabine and Cyclophosphamide in people with Relapsed/refractory Lymphoma and Relapsed/Refractory Leukemia, run by Affiliated Hospital of Nantong University at 1 site in China.

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

This study is a single-center, open-label clinical trial of single-dose of CAR T-cells in subjects with relapsed/refractory hematologic malignancy. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteChina
Study dates
18 Sep 2023to 18 Mar 2026
Phase
Early Phase 1
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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet all of the following criteria to be eligible for the study:
  • Voluntarily participate in the clinical study. The individual or the legal guardian fully understands the study, sign the informed consent form (ICF), and is willing and able to follow and complete all trial procedures.
  • Age ≥ 18 years and < 70 years.
  • Subjects with refractory or relapsed disease after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation) who are not suitable for other treatment options, such as a second stem cell transplant. The definitions of relapsed/refractory lymphoma include one of the following situations:
  • Relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:
  • Primary refractory disease.
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  • First relapse if the initial remission is ≤ 12 months.
  • Relapse or refractory disease after two or more lines of systemic therapy.
  • Relapse or refractory disease after allogeneic transplantation, provided that at the time of enrollment, the subject is at least 100 days post-stem cell transplantation and has not received immunosuppressive drugs for at least 4 weeks prior to enrollment, except for low-dose steroids (≤ 5 mg of prednisone or equivalent).
  • Subjects with Ph+ B-cell ALL, who are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) treatment, or who have relapsed/refractory disease after receiving at least two different TKI treatments, are eligible.
  • Relapsed/refractory B-cell-derived non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) defined as one of the following:
  • No response to first-line treatment (primary refractory disease, excluding subjects intolerant to first-line treatment);
  • Disease progression (PD) as assessed after first-line treatment.
  • Best response of SD after at least 4 cycles of first-line treatment (e.g., 4 cycles of RCHOP), with SD duration not exceeding 6 months after the last dose.
  • No response to second-line or more treatments.
  • PD as the best response to the most recent treatment regimen.
  • Best efficacy of the last line of treatment as SD after at least 2 cycles, with the duration of SD not exceeding 6 months after the last dose.
  • Refractory after autologous stem cell transplant (ASCT).
  • Disease progression or relapse ≤ 12 months post-ASCT (relapsed patients must have biopsy-proven relapse).
  • If salvage treatment is performed after ASCT, the subjects must have no response to or relapsed after the last line of treatment.
  • Relapsed or refractory disease after two or more lines of systemic therapy.
  • Indications included for enrollment in the cohort of anti-CD19-CAR T-cells:
  • CD19+ ALL patients, with bone marrow smear reports showing tumor cells ≥ 5%.
  • CD19+ NHL patients meeting one of the following subtypes:
  • Diffuse large B-cell Lymphoma, not otherwise specified (DLBCL-NOS)
  • Primary mediastinal B-cell lymphoma (PMBCL)
  • Transformed follicular lymphoma (TFL), previously treated for follicular lymphoma and then transformed to refractory DLBCL
  • Mantle cell lymphoma
  • High-grade B-cell lymphoma
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  • Subtypes of lymphoma included for enrollment in the cohort of anti-CD20/30-CAR T-cells:
  • Previously received anti-CD20/30-CAR T-cell therapy, with CD20 expression positive at enrollment.
  • Lymphoma with dual positive expression of CD20/CD30.
  • Indications included for enrollment in the cohort of anti-CD30-CAR T-cell:
  • CD30 positive HL
  • CD30 positive T-cell lymphoma
  • ECOG performance status ≤ 2.
  • Expected survival of at least 12 weeks.
  • Adequate venous access (for apheresis) and no other contraindications for blood cell separation.
  • Laboratory tests during screening must meet the following requirements, and the subject must not have received cell growth factors (long-acting colony-stimulating factors (G-CSF/PEG-CSF) require a 2-week interval) and platelet transfusions within 7 days prior to hematological assessment:
  • Absolute neutrophil count ≥ 1.0×10^9/L (the condition of ALL patients is determined by the investigator).
  • Hemoglobin ≥ 60 g/L (without red blood cell transfusion in the last 14 days).
  • Platelets ≥ 50×10^9/L (the condition of ALL patients is determined by the investigator).
  • Absolute lymphocyte count (ALC) ≥ 0.5×10^9/L.
  • Total serum bilirubin ≤ 1.5× the upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN.
  • Creatinine <1.5×ULN and estimated creatinine clearance ≥60 mL/min.
  • Ejection fraction ≥ 45%, with echocardiogram (ECHO) confirming no pericardial effusion (excluding small or physiological amounts), and electrocardiogram results with no clinical significance.
  • Baseline oxygen saturation > 92% without supplemental oxygen.
  • Women of childbearing potential must have a negative serum or urine pregnancy test result (women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered of childbearing potential).

Who cannot join

  • Subjects are not eligible to participate in this study if they meet any of the following criteria:
  • ALL patients with central nervous system (CNS) abnormalities, including CNS-2 and CNS-3 that are of clinically significant neurological changes:
  • CNS-3 disease is defined as detectable tumor cells in the cerebrospinal fluid (CSF) sample with ≥ 5 WBCs/mm^3, with or without neurological changes.
  • CNS-2 disease is defined as detectable tumor cells in the CSF sample with < 5 WBCs/mm^3 and with neurological changes.
  • Note: Subjects classified as CNS-1 (no detectable tumor cells in CSF) and those with no clinically significant neurological changes classified as CNS-2 are eligible to participate in this study.
  • Brain MRI evidence shows central nervous system lymphoma. Active primary central nervous system DLBL, unless CNS involvement has been effectively treated (i.e., participants are asymptomatic) and there has been a local treatment interval of >4 weeks prior to enrollment.
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  • Presence of active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with CNS involvement.
  • A history of or concurrent presence of other malignancies.
  • Clinically significant cardiac disease or arrhythmias that cannot be controlled with medication.
  • Presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotics for treatment. Uncomplicated urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
  • Positive for hepatitis B (positive for HBsAg, and/or positive for Hepatitis B core antibody and HBV DNA >1000 copies/mL) and hepatitis C (positive for HCV antibodies), syphilis or human immunodeficiency virus (HIV) infection.
  • Presence of any indwelling or drainage catheters (such as percutaneous nephrostomy tubes, indwelling Foley catheters, bile drainage tubes, or pleural/peritoneal/pericardial catheters). The use of specialized central venous access devices, such as Port-A-Cath® or Hickman® catheters, is allowed.
  • Prior medication:
  • Use of clofarabine or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.
  • Injection of live vaccines within 4 weeks prior to enrollment.
  • Donor lymphocyte infusion (DLI) within 28 days prior to enrollment.
  • Any medications used for the treatment of GVHD (such as calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide) within 4 weeks prior to enrollment, or immunosuppressive antibodies (such as anti-CD20, anti-tumor necrosis factor, anti-interleukin-6, or anti-interleukin-6 receptor) used within 4 weeks prior to enrollment.
  • Immune stimulation or immunosuppressive therapy (such as interferon-α, interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or mycophenolic acid) within 4 weeks prior to enrollment.
  • Any systemic immunosuppressive/stimulatory checkpoint molecule therapy within 4 weeks prior to enrollment (such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc.).
  • Use of systemic cytotoxic drugs within 2 weeks prior to enrollment, including daily or weekly low-dose maintenance chemotherapy (such as cyclophosphamide, ifosfamide, bendamustine, chlorambucil, methotrexate, vincristine, etc.).
  • Long-acting growth factors (e.g., pegylated filgrastim) within 14 days prior to leukapheresis, or short-acting growth factors or mobilizing agents (e.g., granulocyte colony-stimulating factor/filgrastim, plerixafor) within 5 days prior to leukapheresis.
  • Radiation therapy within 2 weeks prior to enrollment.
  • Use of pharmacological doses of corticosteroids (>5 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive medications must be avoided within 7 days prior to enrollment.
  • Use of venetoclax (BCL-2 inhibitor) within 4 days prior to leukapheresis.
  • Short-acting targeted therapy (e.g., tyrosine kinase inhibitors) within 72 hours prior to leukapheresis.
  • Idelalisib (oral PI3Kδ inhibitor) within 2 days prior to leukapheresis.
  • Lenalidomide within 1 day prior to leukapheresis.
  • Active graft-versus-host disease (GVHD) ≥ grade 2 on the CIBMTR acute GVHD grading system or requires systemic steroids at doses greater than physiological levels.
  • A history of autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, or systemic lupus) resulting in end-organ injury or requiring systemic immunosuppression/systemic disease-modifying agents within the last 2 years.
  • A history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac diseases within 12 months prior to enrollment.
  • A history of a concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, and Shwachman-Diamond syndrome.
  • A history of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months prior to enrollment. Subjects need to be on preventive anticoagulant medication.
  • A history of other malignancies (except for non-melanoma skin cancer, in situ breast/cervical cancer, and other malignant tumors that have been effectively controlled without treatment in the past five years).
  • Use of other investigational products within 30 days prior to screening.
  • Pregnant or breastfeeding women of childbearing age. Chemotherapy poses potential risks to the fetus or infant. Women who have undergone surgical sterilization or are postmenopausal for at least 2 years are not considered of childbearing potential.
  • Male and female subjects unwilling to practice birth control from the time of consent through 12 months after the completion of lymphodepleting chemotherapy or CAR T cells infusion (whichever is longer).
  • Any medical activities that may interfere with the safety or efficacy assessment of the study treatment.
  • In the investigator's judgment, the subject is unlikely to complete all protocol-required procedures and follow-up visits, or to comply with the requirements for participating in the study.

Trial locations and contacts

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

Hong Liu, MD contact

+86-13951300660

hongliu63@126.com

China1 site, 1 recruiting

  • Affiliated Hospital of Nantong University

    Nantong, Jiangsu, 226001

    Hong Liu, MD, +86-13951300660, hongliu63@126.com

    Hong Liu, MD

    Recruiting

Other trials in China

About this study

Official title: An Exploratory Clinical Study of the Safety and Efficacy of Chimeric Antigen Receptor T-Cells (CAR T-Cells) in Subjects with Relapsed/Refractory Hematologic Malignancy

This study is a single-center, open-label clinical trial of single-dose of CAR T-cells in subjects with relapsed/refractory hematologic malignancy.

Read the detailed description

The study will enroll subjects with relapsed/refractory hematologic malignancy, including lymphoma and leukemia. Subjects will receive a single infusion of CAR T-cells after screening, PBMC collection, and lymphodepleting chemotherapy. Toxicity will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from the National Cancer Institute. Safety of CAR T-cell therapy will be evaluated through laboratory tests, including 12-lead electrocardiograms, vital sign checks, and physical examination etc. Additionally, blood samples will be collected to study cellular pharmacokinetics and explore the effects of cell therapy on ferritin, C-reactive protein, and relevant cytokines.

Being tested
anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells, Fludarabine, Cyclophosphamide
Medical subject headings
Lymphoma, Leukemia

What participants receive

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

  • anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cellsBiological

    Each subject will be infused with single dose. A classic "3+3" dose escalation will be employed.

    anti-CD19-CAR T-cells

    Dose level 1：1x10^5 CAR T cells/kg, Dose level 2：3x10^5 CAR T cells/kg, Dose level 3：1x10^6 CAR T cells/kg

    anti-CD30-CAR T-cells

    Dose level 1：3x10^6 CAR T cells/kg, Dose level 2：6x10^6 CAR T cells/kg, Dose level 3：1x10^7 CAR T cells/kg

    anti-CD20/CD30-CAR T-cells

    Dose level 1：1x10^6 CAR T cells/kg, Dose level 2：3x10^6 CAR T cells/kg, Dose level 3：1x10^7 CAR T cells/kg

  • FludarabineDrug

    Fludarabine will be given at a dose of 25 mg/m^2/day intravenously (IV) for 3 days prior to the infusion of CAR T-cells.

  • CyclophosphamideDrug

    Cyclophosphamide will be given at a dose of 250 mg/m^2/day intravenously (IV) for 3 days prior to the infusion of CAR T-cells.

Study groups in NCT06756321
Study groupRoleWhat they receive
Cyclophosphamide + Fludarabine + CAR T-CellsExperimentalInvestigational product: anti-CD19-CAR T-cells, anti-CD30-CAR T-cell, anti-CD20/CD30-CAR T-cells. Subjects with CD19+ ALL or NHL will be infused with anti-CD19-CAR T-cells. Subjects with CD30+ HL or T-cell lymphoma will be infused with anti-CD30-CAR T-cells. Subjects with CD20+ lymphoma or CD20/CD30 double positive lymphoma who have relapsed after anti-CD19-CAR T-cell therapy will be infused with anti-CD20/CD30-CAR T-cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of CAR T-cells.
Receives: Biological: anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Evaluate safety and tolerability of CAR T-cells

    Proportion of subjects experiencing dose-limiting toxicities (DLT)

    Measured: 28 days after infusion of CAR T-cells

  2. Evaluate the feasibility of administration of CAR T-cells

    The proportion of subjects for whom the desired dose of CAR T-cells can be successfully manufactured

    Measured: 12 months

Secondary outcomes (9)

  1. Adverse events

    Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. AEs will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

    Measured: 12 months

  2. Incidence of cytokine release syndrome (CRS) and neurotoxicity

    Will be assessed using ASTCT Criteria.

    Measured: 12 months

  3. Evaluate cellular kinetics and persistence of CAR T-cells

    Test Copy number of CAR in peripheral blood

    Measured: 28 days after CAR T infusion, after which the evaluation is at the discretion of investigator

  4. Preliminary anti-tumor effect

    Efficacy evaluation will be based on the National Comprehensive Cancer Network guidelines version 1. 2022 (ALL), or Lugano criteria (Lymphoma)

    Measured: 12 months

  5. Overall response rate (ORR)

    Overall response rate (ORR) defined as proportion of subjects achieving partial response or better

    Measured: 12 months

  6. Progression-free survival (PFS)

    Progression-free survival（PFS） defined as the time from the date of CAR T infusion to the first assessment of confirmed disease progression or death, whichever occurs first.

    Measured: Up to 1 year after CAR-T infusion

  7. Overall survival (OS)

    Overall survival defined as the time from the date of CAR T infusion of the subject to death due to any cause

    Measured: Up to 15 years after CAR-T infusion

  8. Evaluate host immunogenicity to CAR T-cells

    Incidence of anti-scFv antibodies

    Measured: 12 months

  9. Evaluate toxicology of CAR T-cells

    Levels of cytokines in serum, including IL-6, IL-10, IFN-γ, TNF-α

    Measured: 28 days after CAR T infusion, after which the evaluation is at the discretion of investigator

Timeline

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

  1. First posted3 Jan 2025
  2. Study start18 Sep 2023
  3. Primary completion18 Mar 2025 (estimated)
  4. Study completion18 Mar 2026 (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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06756321
Sponsor's protocol ID
X01-CN-A1
Status last verified
Dec 2024
First submitted
16 Dec 2024
Last updated
3 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Huang Y, Gong Y, Liu X, Ruan H, Lu J, Kouros-Mehr H, Liu H, Wang H. Case Report: Bispecific CD20/CD30-targeted chimeric antigen receptor T-cell therapy for non-Hodgkin's lymphoma. Front Immunol. 2025 May 8;16:1567149. doi: 10.3389/fimmu.2025.1567149. eCollection 2025.

    PubMed 40406106

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells, Fludarabine and Cyclophosphamide in people with Relapsed/refractory Lymphoma and Relapsed/Refractory Leukemia, run by Affiliated Hospital of Nantong University at 1 site in China.

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 50 inclusion and 38 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 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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 phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 Hong Liu, MD (+86-13951300660, hongliu63@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate safety and tolerability of CAR T-cells (time frame: 28 days after infusion of CAR T-cells). 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 NCT06756321, which also lists 1 linked publication.

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 3 Jan 2025.

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