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B-cell Non Hodgkin LymphomaPhase 2NCT06646666

ARTA-based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment for High-Risk R/R B-NHL Ineligible for HDCT and ASCT

A Phase 2 study testing All-trans retinoic acid, zanubrutinib and radiotherapy in people with B-cell Non Hodgkin Lymphoma, run by Ruijin Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single-center, open-label, prospective study enrolling high-risk (tumor diameter > 4 cm) relapsed/refractory B-NHL patients ineligible for HDCT and ASCT. The treatment consists of ATRA combined with zanubrutinib ± radiotherapy and CAR-T therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-cell Non Hodgkin Lymphoma
What is being tested?
All-trans retinoic acid, zanubrutinib and radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteChina
Study dates
1 Dec 2024to 1 Dec 2027
Phase
Phase 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willingly sign the informed consent form.
  • Age ≥ 18 years, any gender.
  • Histologically confirmed as B-cell non-Hodgkin lymphoma, including:
  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (DLBCL-NOS)
  • Transformed follicular lymphoma (tFL)
  • High-grade B-cell lymphoma (HGBL) with MYC, BCL2, and/or BCL6 rearrangements
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  • High-grade B-cell lymphoma not otherwise specified (HGBL-NOS)
  • Primary mediastinal large B-cell lymphoma (PMBL)
  • Follicular lymphoma grade 3b (FL3b)
  • Patients must have experienced at least one line of treatment for relapsed or refractory disease, meeting the following definitions:
  • Refractory: At least partial response (PR) after the last chemotherapy or relapse within 12 months after autologous transplantation.
  • Relapsed: Complete response (CR) after the last chemotherapy, followed by relapse before enrollment, or relapse or progression 12 months or longer after autologous transplantation.
  • Maximum tumor diameter (long axis) > 4 cm.
  • Evaluator determines that the patient does not meet HDCT/ASCT criteria and meets at least one of the following:
  • Age ≥ 60 years
  • ECOG score = 2
  • FEV1% or DLCO% ≤ 60%
  • LVEF < 50%
  • Creatinine clearance < 60 mL/min
  • ALT or AST > 2× upper limit of normal (ULN)
  • Patient unwilling to receive high-dose chemotherapy and autologous stem cell transplantation.
  • Measurable target lesions: lymph nodes ≥ 15 mm in longest diameter, or extranodal lesions > 10 mm.
  • Expected survival ≥ 12 weeks.
  • Laboratory tests must meet the following requirements at screening:
  • Lymphocyte count ≥ 0.1 × 10^9/L
  • Hemoglobin ≥ 80 g/L
  • Platelets ≥ 50 × 10^9/L
  • ALT/AST ≤ 5 × ULN and total bilirubin < 2 × ULN
  • Creatinine clearance ≥ 30 mL/min
  • Lung function: ≤ CTCAE grade 1 dyspnea, and oxygen saturation (SpO2) ≥ 92% in room air.
  • LVEF ≥ 40%
  • Patients with primary central nervous system lymphoma are allowed (secondary CNS lymphoma is not allowed).
  • Sufficient venous access for apheresis, and no other contraindications for blood cell separation; female participants of childbearing potential must have a negative pregnancy test at screening.

Who cannot join

  • History of allergy to any component of the cellular product or study treatment.
  • History of allogeneic hematopoietic stem cell transplantation.
  • History of organ transplantation.
  • Patients with active viral hepatitis requiring treatment, including:
  • Chronic HBV carriers with HBV DNA ≥ 500 IU/mL.
  • Positive HCV RNA in patients with positive HCV antibodies.
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  • Positive HIV antibodies (HIV-Ab).
  • Positive Treponema pallidum antibodies (TP-Ab).
  • Elevated CMV DNA or EBV DNA above normal limits.
  • Clinical significance of CNS diseases
  • Presence of active primary central nervous system lymphoma.
  • Prior treatment with other genetically modified T-cell therapies or CAR-T therapies.
  • Severe genetic diseases or autoimmune diseases (e.g., systemic lupus erythematosus).
  • Thromboembolic events (e.g., myocardial infarction, pulmonary embolism, deep vein thrombosis) within 6 months prior to screening.
  • History of malignancies other than the indication for this trial within the last 5 years, except for in situ cancers (e.g., cervical, bladder, breast) or non-melanoma skin cancer.
  • Active infections requiring systemic treatment or uncontrolled infections.
  • Received lenalidomide, calcineurin inhibitors, chemotherapy (e.g., methotrexate, cyclophosphamide, ifosfamide, nitrogen mustard, or melphalan), mycophenolate, thalidomide, immunosuppressive antibodies (e.g., anti-TNF, anti-IL6, or anti-IL6R), radiation therapy, or any drug that binds FKBP12 (e.g., rapamycin, tacrolimus, everolimus) within 4 weeks prior to PBMC collection.
  • Pregnant or breastfeeding women, or men or women of childbearing potential unwilling to use contraception during the trial and for 2 years after RJ CAR-T 002 cell infusion.
  • Participation in other drug clinical trials (e.g., new drug trials, registrational studies, investigator-initiated trials) within 4 weeks prior to PBMC collection.
  • Researcher's judgment that the patient is unsuitable for the trial (e.g., poor compliance, drug abuse).
  • Vaccination with live or attenuated vaccines within 3 months prior to PBMC collection, or expected vaccination during the trial.

Trial locations and contacts

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

Weili Zhao contact

+862164370045

zwl_trial@163.com

China1 site

  • Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

    Shanghai

Other trials in China

About this study

Official title: Efficacy and Safety of All-trans Retinoic Acid (ATRA)-Based Chemo-free Bridging/Maintenance Therapy in CAR-T Treatment of High-risk Relapsed/Refractory B-NHL Ineligible for High-dose Chemotherapy （HDCT） and Autologous Stem Cell Transplantation （ASCT）

This is a single-center, open-label, prospective study enrolling high-risk (tumor diameter > 4 cm) relapsed/refractory B-NHL patients ineligible for HDCT and ASCT. The treatment consists of ATRA combined with zanubrutinib ± radiotherapy and CAR-T therapy. Based on the efficacy at day 28 post-CAR-T infusion, patients achieving CR will receive 3 months of ATRA and zanubrutinib, while those with PR will receive 3 months of zanubrutinib plus 2 years of ATRA and a PD-1 inhibitor. Patients with stable disease or progression will discontinue. The primary endpoint is the 3-month CR rate following CAR-T infusion.

Being tested
All-trans retinoic acid, zanubrutinib, radiotherapy, CAR-T, PD-1 inhibitor
Medical subject headings
Lymphoma, B-Cell

What participants receive

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

  • All-trans retinoic acidDrug

    10mg，tid，po (After apheresis and continued until post-infusion)

  • zanubrutinibDrug

    160mg，bid，po (prior to apheresis and continued until post-infusion)

  • radiotherapyRadiation

    If the patient's specific lesions are suitable for radiotherapy

  • CAR-TDrug

    CAR-T cell therapy

  • PD-1 inhibitorDrug

    IV 200 mg on D1, Q3W

Study groups in NCT06646666
Study groupRoleWhat they receive
ARTA-based Chemo-free bridging therapy to CAR-T and maintenance therapy post CAR-TExperimentalNot described
Receives: Drug: All-trans retinoic acid; Drug: zanubrutinib; Radiation: radiotherapy; Drug: CAR-T; Drug: PD-1 inhibitor

What is being measured

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

  1. Complete Response (CR) Rate at 3-month

    Complete response rate at 3-month is defined as the incidence of subjects achieving complete remission (CR) within 3 months after CAR-T infusion according to the Lugano Classification (Cheson et al, 2014), as determined by study investigators.

    Measured: 3 months post CAR-T infusion

Secondary outcomes (3)

  1. Progression-Free Survival (PFS)

    PFS is defined as the time from the CAR-T infusion date to the date of disease progression or death from any cause.

    Measured: 2 years post CAR-T infusion

  2. Overall Survival (OS)

    OS is defined as the time from CAR-T infusion to the date of death from any cause.

    Measured: 2 years post CAR-T infusion

  3. Adverse Events rate as assessed by CTCAE version 5.0

    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Measured: 2 years post CAR-T infusion

Timeline

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

  1. First posted17 Oct 2024
  2. Study start1 Dec 2024 (estimated)
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Dec 2027 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06646666
Sponsor's protocol ID
CAR-T 002
Status last verified
Oct 2024
First submitted
15 Oct 2024
Last updated
1 Nov 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing All-trans retinoic acid, zanubrutinib and radiotherapy in people with B-cell Non Hodgkin Lymphoma, run by Ruijin Hospital 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 33 inclusion and 21 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: opening soon, as of the sponsor's last update on 1 Nov 2024. 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?

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 Weili Zhao (+862164370045, zwl_trial@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) Rate at 3-month (time frame: 3 months post CAR-T infusion). 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 NCT06646666.

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 1 Nov 2024.

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