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Non-Hodgkin's LymphomaPhase 1NCT06206902

F01 in the Treatment of Relapsed/Refractory Non-hodgkin's Lymphoma

A Phase 1 study testing After preconditioning with chemotherapy, F01 will be evaluated. in people with Non-Hodgkin's Lymphoma, run by Shanghai Simnova Biotechnology Co.,Ltd. at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a multicenter, open, Phase I clinical study to evaluate the safety and tolerability of F01 in subjects with relapsed/refractory non-Hodgkin lymphoma, and to determine MTD and/or RD. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Hodgkin's Lymphoma
What is being tested?
After preconditioning with chemotherapy, F01 will be evaluated.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
2 sitesChina
Study dates
Apr 2024to Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years old, gender unlimited.
  • ECOG score 0-2 points.
  • Large B-cell lymphoma or follicular lymphoma grade 3b was confirmed by histopathology.Large B-cell lymphomas include the following types as defined by WHO2016:
  • Diffuse large B lymphoma (DLBCL), non-specific type (NOS);
  • Large B-cell lymphoma rich in T cells/histiocytic cells;
  • EBV positive DLBCL, non-specific type (NOS);
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  • Primary mediastinal (thymus) large B-cell lymphoma;
  • High-grade B-cell lymphoma, non-specific type (NOS) and high-grade B-cell lymphoma with MYC and BCL2 or BCL6 rearrangement;
  • Follicular lymphoma or other inert lymphoma transformed DLBCL.
  • Must have been previously treated with at least 2-line systemic anti-B-cell lymphoma. Participants must have received at least one course of anthracycline-based chemotherapy (except when absolutely contraindicated due to cardiac dysfunction) and at least one course of anti-CD20 immunotherapy (except in CD20-negative subjects or contraindicated due to severe toxicity).
  • Induction + consolidation + transplantation + maintenance treatment is a one-line system of treatment;
  • Anti-CD20 monotherapy does not count as 1-line systemic therapy;
  • Local radiotherapy does not count as 1-line systemic therapy.
  • Patients who have previously received targeted CD19 therapy (including monoclonal antibody, double antibody, CAR-T, experimental therapy, etc.) should provide histophistological reports during screening stage to confirm that CD19 expression is still present in lymphoma tissues after the last targeted CD19 therapy.
  • Imaging evidence indicates recurrent or refractory disease.
  • Definition of relapse: partial response (PR) or above achieved after the last treatment, with disease progression after treatment (except for those who meet the definition of refractory);
  • Refractory is defined as the failure to achieve a partial response (PR) or above from the last treatment, or relapse within 6 months after the last treatment regimen, or relapse within 12 months after autologous hematopoietic stem cell transplantation (ASCT). (If salvage therapy is performed after ASCT, subjects must have a response < PR to terminal therapy.).
  • According to Lugano 2014 lymphoma efficacy evaluation criteria (Cheson 2014), there is at least one measurable lesion (a measurable lesion is defined as a lymph node lesion with a diameter greater than 1.5cm and an extra-lymph node lesion with a diameter greater than 1.0cm).
  • Lesions that have previously received radiotherapy are only considered measurable if there is clear evidence of disease progression after completion of radiotherapy.
  • The expected survival is greater than 3 months.
  • Blood routine within 7 days from eluvial pre-treatment chemotherapy should meet the following requirements:
  • Absolute value of neutrophil (ANC) ≥ 1.0×109/L;
  • Hemoglobin (Hb) ≥ 80g/L;
  • Platelet count (PLT) ≥ 50×109/L.
  • Adequate liver, kidney, lung and heart function, defined as:
  • Serum ALT and AST ≤ 2.5 times the upper limit of normal;
  • Total bilirubin ≤ 1.5 times the upper limit of normal, except those with Gilbert syndrome, whose total bilirubin must ≤ 3.0 times the upper limit of normal;
  • Creatinine clearance (estimated by Cockcroft Gault formula) (Appendix 2) ≥60ml/min;
  • Under indoor ventilation conditions, the blood oxygen saturation in the non-oxygen state is ≥ 92%; There was no clinically significant pleural effusion;
  • Left ventricular ejection fraction ≥ 50%; Echocardiography confirmed no clinically significant pericardial effusion. No clinically significant abnormalities were found in the ECG.
  • Subjects receiving hematopoietic growth factor support therapy, including erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-colony-stimulating factor (GM-CSF), and platelet agonist (TPO), There must be a 2-week interval between the last growth factor support treatment and the screening period evaluation; Screening platelet assessment should be at least 1 week away from the last platelet transfusion, and screening hemoglobin assessment should be at least 2 weeks away from the last red blood cell transfusion.
  • During the screening period, the serum pregnancy test results of fertile female subjects must be negative (women who have been surgically sterilized or have been menopausal for at least 2 years are considered not fertile). Fertile female subjects and male subjects must use highly effective contraceptive methods throughout the clinical study period and within 1 year after the last study treatment; At the same time, a commitment should be made not to donate eggs (egg cells, oocytes)/sperm for assisted reproduction within 1 year after the last study treatment.
  • Voluntarily participate in clinical trials and sign informed consent.

Who cannot join

  • Subjects with known allergic reactions, hypersensitivities, intolerances, or contraindications to F01 or any component of the drugs that may be used in the study, including fludarabine, cyclophosphamide, and tocilizumab, or who have previously experienced severe allergic reactions.
  • Primary central nervous system lymphoma.
  • Subjects with gastrointestinal lymphoma who had a history of ≥ grade 3 gastrointestinal bleeding in the 3 months prior to screening and those at risk of developing ≥ grade 3 gastrointestinal bleeding as assessed by investigators (CTCAE, version 5.0).
  • Subjects with a history of central nervous system lymphoma, lymphoma cells found in cerebrospinal fluid, and previous imaging findings of intracranial involvement of lymphoma could not be enrolled.
  • Performed allogeneic hematopoietic stem cell transplantation.
  • Autologous hematopoietic stem cell transplantation was performed within 3 months before eluvial pre-treatment chemotherapy.
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  • Subjects who have previously received CD19-targeted CAR-NK therapy; The best efficacy of previous targeted CD19 CAR-T therapy < PR.
  • Major surgery or live vaccination within 28 days prior to screening.
  • Received the following anti-tumor therapy within the specified time frame before eluvial pre-treatment chemotherapy:
  • Received small molecule targeted therapy within 3 weeks or 5 half-lives (whichever is longer);
  • Receiving large molecule drug therapy within 4 weeks or 5 half-lives, whichever is longer (4 weeks for anti-CD20 antibody);
  • Received cytotoxic therapy or modern Chinese medicine with anti-tumor effects within 3 weeks (liposomal adriamycin washout period was 4 weeks);
  • Have received experimental therapy within 4 weeks (except for explicit placebo control);
  • Received local palliative radiotherapy within 2 weeks.
  • At the time of screening, any aes associated with previous anti-lymphoma therapy have not returned to ≤ grade 1 or baseline (CTCAE version 5.0) (except for hair loss, blood routine and blood biochemical related AEs; Blood routine and blood biochemical test values refer to the inclusion criteria Article 9 and 10).
  • Previous CNS disease, such as seizures, cerebrovascular accidents (ischemia/bleeding), dementia, cerebellar disease, or any CNS related autoimmune disease.
  • At the time of screening, confirmed systemic autoimmune diseases requiring maintenance treatment or confirmed systemic autoimmune diseases were in the active phase.
  • Unstable cardiovascular function:
  • Myocardial infarction occurred within 6 months prior to screening;
  • Unstable angina occurred within 3 months prior to screening;
  • Uncontrolled, clinically significant arrhythmias (e.g., persistent ventricular tachycardia, ventricular fibrillation, torsades de pointes arrhythmia );
  • Mobitz II degree II or III degree atrioventricular block;
  • New York Heart Function Society classification ≥3 congestive heart failure;
  • Poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) or accompanied by hypertensive crisis or hypertensive encephalopathy;
  • Active hepatitis B virus (HBV), hepatitis C virus (HCV) infection at screening time. Admission of HBsAg positive and/or HBcAb positive but HBV-DNA negative, and/or HCVAb positive but HCV-RNA negative subjects (if the study center report includes a reference value range, the upper limit of normal HBV-DNA and HCV-RNA testing is based on the test values at each study center). Higher than the upper limit of the detection value is defined as "positive"; If the research center report only shows "negative/positive", "positive" is subject to the test report result).
  • Known serum HIV-positive or active HIV infection history, and syphilis screening antibody positive.
  • There is an active, uncontrolled infection that requires intravenous treatment with antibiotics, antiviral or antifungal agents within 14 days prior to eluvial pre-treatment chemotherapy; However, these drugs can be used for preventive treatment (including intravenous medication).
  • Malignant tumors that require treatment or have evidence of recurrence within 2 years prior to screening (except non-melanoma skin cancer that has been surgically removed, cured cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, and ductal carcinoma in situ of the breast). However, subjects with tumors that had received >2 years of prior radical therapy and had no evidence of recurrence were admitted.
  • Use of drug combinations/combination therapies expressly prohibited by the protocol during screening.
  • The investigator believes that there is any life-threatening disease, medical condition, or organ system dysfunction that may affect the subject's safety or study compliance.

Trial locations and contacts

2 sites in 1 country.

Director Clinical Trial Disclosure Simnova contact

021-68099999

Disclosure@simnovabio.com

China2 sites, 2 recruiting

  • The First Affiliated Hospital Zhejiang University School of Medicine

    Hangzhou, Zhejiang

    Hongyan Tong, 13958122357, hongyantong@aliyun.com

    Recruiting

  • Union Hospital Tongji Medical College Huazhong University of Science and Technology

    Wuhan, Hubei

    Yu Hu, 139 8618 3871, dr_huyu@126.com

    Heng Mei, 138 8616 0811, mayheng@126.com

    Recruiting

Other trials in China

About this study

Official title: A Multicenter, Open Phase I Study to Evaluate the Safety and Pharmacokinetic Profile of F01 in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma

This is a multicenter, open, Phase I clinical study to evaluate the safety and tolerability of F01 in subjects with relapsed/refractory non-Hodgkin lymphoma, and to determine MTD and/or RD.

Read the detailed description

Approximately 55 participants with relapsed and/or refractory large B-cell lymphoma and follicular lymphoma stage 3b are planned to enroll. This study is divided into two stages: dose escalation and dose extension. In the phase of dose escalation, a single dose escalation study will be carried out first, and then multiple dose escalation studies will be carried out. In the dose expansion phase, up to 3 subjects who had previously received CD19-targeted CAR T cell therapy may enroll.

After the completion of the single dose escalation study, SRC will determine the MTD and/or RD of the single dose escalation phase based on the safety, pharmacokinetic profile (if applicable), immunogenicity, efficacy, and other data available at the time for each dose group. SRC will also determine whether the study will continue with multiple dose escalation studies or a single dose is sufficient to meet therapeutic needs. Multiple dose escalation can be skipped to provide recommendations for dose expansion phase studies based directly on single dose MTD and/or RD doses. After fully evaluating all opinions and data, the sponsor may choose to: 1) Multiple dose escalation studies are not conducted, and the MTD and/or RD doses with a single dose increase are directly entered into the dose expansion phase. In this case, enrolled subjects are continued to receive a single dose during the dose expansion phase to further confirm the safety and efficacy of subjects under RD dose; 2) After the single dose increment, enter the multi-dose increment study, and enter the dose extension phase after confirming the MTD and/or RD doses of multiple doses.

Being tested
After preconditioning with chemotherapy, F01 will be evaluated.
Keywords
NK, Non-Hodgkin's Lymphoma
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

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

  • After preconditioning with chemotherapy, F01 will be evaluated.Drug

    Biological: 0.5-3×10^9 CAR+NK Cells, Treatment follows a lymphodepletion Drug: Fludarabine: 30 mg/m^2 (D-5~D-3) Drug: Cyclophosphamide: 300 mg/ m^2 (D-5~D-3)

Study groups in NCT06206902
Study groupRoleWhat they receive
Assigned InterventionsExperimentalNot described
Receives: Drug: After preconditioning with chemotherapy, F01 will be evaluated.

What is being measured

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

  1. Safety of F01 cells

    The incidence, nature and severity of all adverse events, serious adverse events, and abnormal laboratory test results

    Measured: Up to 24 months

  2. Safety of F01 cells

    Incidence of DLT

    Measured: Up to 1 month

Secondary outcomes (14)

  1. Response rate (ORR) of F01 cells

    Optimal objective response rate (ORR), 3-month ORR

    Measured: From 1 to 24 months after infusion

  2. Duration of response (DOR) of F01 cells

    Duration of response (DOR)

    Measured: From 1 to 24 months after infusion

  3. Progression-free survival (PFS) of F01 cells

    Progression-free survival (PFS)

    Measured: From 1 to 24 months after infusion

  4. Overall survival (OS) of F01 cells

    Overall survival (OS)

    Measured: From 1 to 24 months after infusion

  5. Maximum concentration of F01 cells

    Maximum concentration

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  6. Cmax of F01 cells

    Gene copy number amplification (Cmax)

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  7. Tmax of F01 cells

    Time to reach the maximum concentration (Tmax)

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  8. AUC0-last of F01 cells

    The area under the drug curve AUC0-last

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  9. Clast of F01 cells

    Last detectable concentration point (Clast)

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  10. Tlast of F01 cells

    Time of the last detectable concentration (Tlast)

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  11. Dynamic changes of cytokine levels

    The dynamic changes of cytokine levels in peripheral blood of subjects at baseline and after administration

    Measured: From 1 to 24 months

  12. Anti-CAR and IL-15 antibodies (ADA)

    The number of cases, positive rates, and duration of detection of anti-CAR and IL-15 antibodies (ADA) in subjects' serum at baseline and after administration

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

  13. Peripheral blood lymphocyte subsets

    Dynamic changes of peripheral blood lymphocyte subsets compared with baseline after administration

    Measured: From 1 to 24 months

  14. Detection rate of replicable virus

    Detection rate of replicable virus

    Measured: From 1 to 15 years after infusion or after learning of undetectable results

Timeline

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

  1. First posted16 Jan 2024
  2. Study startApr 2024 (estimated)
  3. Primary completionJan 2025 (estimated)
  4. Study completionDec 2025 (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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06206902
Sponsor's protocol ID
SNC 103-CD19CAR NK-101
Status last verified
Dec 2023
First submitted
18 Dec 2023
Last updated
23 Feb 2024
Results posted
No
Data monitoring committee
No
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 study testing After preconditioning with chemotherapy, F01 will be evaluated. in people with Non-Hodgkin's Lymphoma, run by Shanghai Simnova Biotechnology Co.,Ltd. at 2 sites 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 33 inclusion and 30 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: status not confirmed, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

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.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Director Clinical Trial Disclosure Simnova (021-68099999, Disclosure@simnovabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of F01 cells (time frame: Up to 24 months). 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 NCT06206902.

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 23 Feb 2024.

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