B-cell Non-Hodgkin's LymphomaPhase 1NCT06314828
A Tolerability, Safety and Efficacy Study of RJMty19 in Subjects With Relapsed or Refractory B-NHL
A Phase 1 study testing RJMty19 (CD19-CAR-DNT cells) in people with B-cell Non-Hodgkin's Lymphoma, run by Guangdong Ruishun Biotech Co., Ltd.
Trial summary
This is a Phase 1, open-label, single-arm study to evaluate tolerability, safety and efficacy of RJMty19 in adult subjects with r/r B-NHL. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- B-cell Non-Hodgkin's Lymphoma
- What is being tested?
- RJMty19 (CD19-CAR-DNT cells)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 20 May 2024to 20 May 2027
- Phase
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily sign an ICF and expect to complete the subsequent follow-up.
- Aged 18 to 65 years (including cut-offs), regardless of gender.
- B-cell non-Hodgkin's lymphoma diagnosed as CD19-positive by cytology or histopathology according to WHO 2022 criteria, including pathologically confirmed (1) diffuse large B-cell lymphoma, non-specific type (DLBCL, NOS); (2) follicular lymphoma histopathologically graded as grade 3b (FL3b); (3) follicular lymphoma with diffuse large B-cell transformation; (4) primary mediastinal large B-cell lymphoma (PMBCL); (5) high-grade B-cell lymphoma (HGBCL).
- Relapsed/refractory B-cell non-Hodgkin's lymphoma, provided one of the following conditions is met:
- Definition of relapse: Relapse after achieving remission (PR and CR) with second-line or higher therapy;
- Definition of refractory:
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- No response to second-line or more therapy: The best efficacy of last therapy is PD or SD (SD requires at least 2 cycles of treatment);
- Recurrence (must have biopsy-proven recurrence) or progression within 12 months of autologous stem cell transplantation (ASCT) . If salvage therapy, no response to last therapy (SD or PD).
- Subjects must have received adequate treatment in the past, which should include the following treatments:
- Anti-CD20 monoclonal antibody, unless the investigator determines that the tumor is CD20 negative;
- Chemotherapy containing anthracycline drugs;
- For subjects with transformed follicular lymphoma (tFL) who have been previously treated with follicular lymphoma (FL) chemotherapy and with transformation to DLBCL show refractory to chemotherapy.
- ECOG performance status 0 to 1.
- The presence of a measurable lesion that meets one of the following criteria:
- The long axis of the lymph node lesion exceeds 15 mm in length (the short axis is measurable);
- The long and short axes of the extralymph node lesion exceed 10 mm in length.
- ALaboratory results within 7 days prior to Lymphodepletion need to meet the following criteria:
- Coagulation function:
- Activated partial thromboplastin time ≤ 1.5 times the upper limit of normal (ULN);
- Prothrombin time (PT) ≤ 1.5 times ULN;
- Liver function:
- Glutathione aminotransferase (AST) ≤ 5 times the upper limit of normal (ULN);
- Glutamic aminotransferase (ALT) ≤ 5 times the upper limit of normal (ULN);
- Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome;
- Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included.
- Renal function:
- Serum creatinine ≤ 1.5 times ULN or a creatinine clearance ≥ 60 ml/min;
- Complete blood count (No blood transfusion treatment received within 7 days prior to examination):
- Haemoglobin ≥ 80 g/L;
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L;
- A platelet count ≥ 50 x 10^9/L;
- Cardiopulmonary function:
- Left ventricular ejection fraction (LVEF) ≥ 45%;
- Oxygen saturation ≥ 91%;
- Female subjects with of childbearing potential should have a negative pregnancy test during the screening period. Any male and female subjects of childbearing potential must agree to use an effective contraception method for at least six months from the time that they sign the informed consent form until the end of the cell infusion. Female subjects without childbearing potential (meeting at least 1 of the following criteria) is described below:
- Have undergone a hysterectomy or bilateral oophorectomy;
- Medically recognised ovarian failure;
- Medically recognised as post-menopausal (at least 12 consecutive months of menopause without pathological or physiological cause).
Who cannot join
- Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer
- Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after >1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders.
- Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
- Subjects who are receiving systemic steroids prior to screening and who are judged by the investigator to require long-term treatment with systemic steroids during the treatment period (except for inhaled or topical use).
- Previous organ transplantation or preparation for organ transplantation (except for haematopoietic stem cell transplantation).
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- Persons with acute/chronic Graft-vs-Host Disease (GvHD).
- Patients have received a haematopoietic stem cell transplant within 2 months prior to screening.
- Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)).
- Clinically significant active cerebrovascular diseases (such as cerebral edema, posterior reversible encephalopathy syndrome).
- Patients with a life expectancy of less than 3 months.
- Subjects have participated in other interventional clinical studies within 3 months prior to screening.
- Received attenuated live vaccine within 6 weeks prior to lymphodepletion.
- The subjects have contraindications or hypersensitivity reactions to fludarabine, cyclophosphamide, etoposide, tocilizumab, investigational product and its ingredients.
- Remaining within the washout period of other antitumor treatments prior to lymphodepletion.
- Patients who, in the investigator's judgment and/or clinical criteria, have a contraindication to any of the study procedures or have other medical conditions that may place them at unacceptable risk.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 1, Open-label, Single Arm Clinical Trial to Evaluate the Tolerability, Safety and Efficacy of RJMty19 in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)
This is a Phase 1, open-label, single-arm study to evaluate tolerability, safety and efficacy of RJMty19 in adult subjects with r/r B-NHL.
Read the detailed description
The study was based on an accelerated titration and "3+3" design with a dose-escalation phase and a dose-expansion phase, and was designed to assess the safety, maximum tolerated dose, pharmacokinetic profile, and initial efficacy of RJMty19 in subjects with r/r B-NHL after second-line treatment or above.
- Conditions
- B-cell Non-Hodgkin's Lymphoma
- Being tested
- RJMty19 (CD19-CAR-DNT cells)
- Keywords
- off-the-shelf cell product, CAR-DNT, Cell Therapy, B-NHL
- 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.
RJMty19 (CD19-CAR-DNT cells)Biological
Lentiviral vector-transducted double negative T cells (DNT) to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide, fludarabine and Etoposide lymphodepleting chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| RJMty19 (CD19-CAR-DNT Cells) | Experimental | The trial is divided into two parts: Part A is a dose escalation trial with four dose groups (5×10^6 CAR+ cells/kg, 1×10^7 CAR+ cells/kg, 2×10^7 CAR+ cells/kg and 4×10^7 CAR+ cells/kg at day 0), with 8-24 patients planned to be enrolled. Part B is a dose-expansion trial in which 3~6 patients will receive RJMty19 infusions at RP2D dose levels. Receives: Biological: RJMty19 (CD19-CAR-DNT cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-Limiting Toxicity (DLT)
To evaluate the safety, tolerability, and determine the recommended dosage of RJMty19 for R/R B-NHL subjects
Measured: Up to 28 days
Maximum Tolerated Dose (MTD)
MTD is the highest dose for DLT in ≤1/6 subjects
Measured: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Measured: Up to 28 days
Secondary outcomes (10)
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of CD19-CAR-DNT cells amplified in the peripheral blood (Cmax, detected by qPCR and Flow Cytometry).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by qPCR and Flow Cytometry).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the peak plasma time (Tmax). Tmax is defined as the time to reach the highest concentration (Tmax, detected by qPCR and Flow Cytometry).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (T1/2)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of CD19-CAR-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by qPCR and Flow Cytometry).
Measured: Up to 90 days
Overall Response Rate
The proportion of CR or PR patients as assessed by investigators based on Lugano 2014 Response Assessment
Measured: Up to 2 years
Disease Control Rate
The percentage of PR, CR and SD patients in the total patient population
Measured: Up to 2 years
Duration of Response
The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Measured: Up to 2 years
Progression Free Survival
The length of time that a participant's disease did not progress during or after RJMty19 infusion.
Measured: Up to 2 years
Overall Survival
From the date of entry into the clinical study until death from any cause
Measured: Up to 15 years
Overall Response Rate at 3 months
The percentage of PR and CR patients in the total patient population at 3 months
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start20 May 2024 (estimated)
- Primary completion20 May 2025 (estimated)
- Study completion20 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Ruishun Biotech Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital, Southern Medical University, China, Beijing GoBroad Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06314828
- Sponsor's protocol ID
- RJMty19-B-NHL002
- Status last verified
- Jan 2024
- First submitted
- 11 Mar 2024
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Single Arm Clinical Trial to Evaluate the Tolerability, Safety and Efficacy of RJMty19 in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT06314828
- Acronym / sponsor ID
- RJMty19-B-NHL002
- Conditions
- B-cell Non-Hodgkin's Lymphoma
- Keywords
- off-the-shelf cell product, CAR-DNT, Cell Therapy, B-NHL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Guangdong Ruishun Biotech Co., LtdIndustry (pharma, biotech, devices)
- Collaborators
- Ruijin Hospital, Southern Medical University, China, Beijing GoBroad Hospital
- Study start
- 20 May 2024 (estimated)
- Primary completion
- 20 May 2025 (estimated)
- Study completion
- 20 May 2027 (estimated)
- First posted
- 18 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1, open-label, single-arm study to evaluate tolerability, safety and efficacy of RJMty19 in adult subjects with r/r B-NHL.
Detailed description
The study was based on an accelerated titration and "3+3" design with a dose-escalation phase and a dose-expansion phase, and was designed to assess the safety, maximum tolerated dose, pharmacokinetic profile, and initial efficacy of RJMty19 in subjects with r/r B-NHL after second-line treatment or above.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RJMty19 (CD19-CAR-DNT Cells) | Experimental | Biological: RJMty19 (CD19-CAR-DNT cells)The trial is divided into two parts: Part A is a dose escalation trial with four dose groups (5×10^6 CAR+ cells/kg, 1×10^7 CAR+ cells/kg, 2×10^7 CAR+ cells/kg and 4×10^7 CAR+ cells/kg at day 0), with 8-24 patients planned to be enrolled. Part B is a dose-expansion trial in which 3~6 patients will receive RJMty19 infusions at RP2D dose levels. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Voluntarily sign an ICF and expect to complete the subsequent follow-up.
- Aged 18 to 65 years (including cut-offs), regardless of gender.
- B-cell non-Hodgkin's lymphoma diagnosed as CD19-positive by cytology or histopathology according to WHO 2022 criteria, including pathologically confirmed (1) diffuse large B-cell lymphoma, non-specific type (DLBCL, NOS); (2) follicular lymphoma histopathologically graded as grade 3b (FL3b); (3) follicular lymphoma with diffuse large B-cell transformation; (4) primary mediastinal large B-cell lymphoma (PMBCL); (5) high-grade B-cell lymphoma (HGBCL).
- Relapsed/refractory B-cell non-Hodgkin's lymphoma, provided one of the following conditions is met:
- Subjects must have received adequate treatment in the past, which should include the following treatments:
Key exclusion criteria (16 listed)
- Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer
- Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after >1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders.
- Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
- Subjects who are receiving systemic steroids prior to screening and who are judged by the investigator to require long-term treatment with systemic steroids during the treatment period (except for inhaled or topical use).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RJMty19 (CD19-CAR-DNT cells)Lentiviral vector-transducted double negative T cells (DNT) to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide, fludarabine and Etoposide lymphodepleting chemotherapy. | Biological | RJMty19 (CD19-CAR-DNT Cells) |
Primary outcome
Dose-Limiting Toxicity (DLT)
Time frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of RJMty19 for R/R B-NHL subjects
Maximum Tolerated Dose (MTD)
Time frame: Up to 28 days
MTD is the highest dose for DLT in ≤1/6 subjects
Incidence of abnormalities
Time frame: Up to 28 days
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
10 secondary outcomes
Pharmacokinetics (PK) indicator (Cmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (T1/2)
Time frame: Up to 90 days
Overall Response Rate
Time frame: Up to 2 years
Disease Control Rate
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Progression Free Survival
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 15 years
Overall Response Rate at 3 months
Time frame: Up to 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RJMty19 (CD19-CAR-DNT cells) in people with B-cell Non-Hodgkin's Lymphoma, run by Guangdong Ruishun Biotech Co., Ltd.
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 38 inclusion and 16 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 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
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, MD,PhD (+862164370045 ext. 610707, zhao.weili@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2024.