Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 PositivePhase 1A-02NCT04215016
Safety of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells in Adult Patients With Diffuse Large B-cell Lymphoma
A Phase 1 study testing Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells in people with Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive, run by Fujian Medical University at 1 site in China.
Trial summary
This is a single-arm, open-label, dose escalation, phase I study, aiming to evaluate the safety and efficacy of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific Chimeric Antigen Receptor (CAR) T-cells in patient with relapsed or refractory diffuse B cell lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive
- What is being tested?
- Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- Dec 2019to Dec 2024
- 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
- The subject or her/his legally guardian(s) must sign the informed consent form approved by the Institutional Ethics Committee (IEC) prior to any screening procedures;
- Subjects aged 18 years or older with relapsed or refractory DLBCL (primary mediastinal large B-cell lymphoma and transformed follicular lymphoma included), of which refractory is defined as:
- Have no response to the recent treatment including:
- The best response to the treatment regimen is progressive disease (PD) ,or
- stable disease (SD) which maintained less than 6 months after the last treatment, or
- not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:
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- progressive disease after ASCT or relapse within 12 months (relapse must be confirmed by biopsy), or
- If remedial treatment is given after ASCT, the subject must have no response or relapse after the last treatment.
- Subjects who have previously received ≥2 lines treatment, and at least including:
- Anti-CD20 monoclonal antibody(rituximab), unless the CD20 negative;
- A chemotherapy regimen containing anthracyclines;
- The DLBCL patients who transformed from follicular lymphoma must have previously received chemotherapy for follicular lymphoma and have developed chemotherapy-refractory diseases after transform to DLBCL.
- Confirmation for either CD19 or CD20 positivity using immunohistochemistry or flow cytometry;
- According to the initial evaluation, staging and response assessment of Hodgkin's and non-Hodgkin's lymphoma -the Lugano Classification (2014), there is at least one measurable lesion at baseline;
- Life expectancy ≥12 weeks;
- Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening;
- Adequate organ function:
- Renal function defined as:
- A serum creatinine of ≤1.5 × Upper Limit of Normal (ULN), or;
- Estimated Glomerular Filtration Rate (eGFR) ≥60 ml/min/1.73m2；
- Liver function defined as:
- ALT≤ 5 × Upper Limit of Normal (ULN) for age, and;
- Total bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN.
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and blood oxygen saturation > 91% on room air;
- Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA);
- Adequate bone marrow reserve without transfusions defined as:
- Absolute neutrophil count (ANC) >1×10^9 /L；
- Absolute lymphocyte count (ALC) ≥0.3×10^9 /L；
- Platelets ≥50×10^9 /L;
- Hemoglobin > 8.0 g/dl;
- Must have an apheresis product of non-mobilized cells or peripheral blood harvested cells accepted for manufacturing
- Subjects who use the following drugs should meet the following criteria:
- Steroids: Therapeutic doses of steroids must be stopped 2 weeks prior to A-02 infusion. However, the following physiological replacement doses of steroids are allowed: < 6 - 12 mg/m^2/day hydrocortisone or equivalent;
- Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks prior to sign the informed consent form;
- Anti-proliferative therapy other than pretreatment chemotherapy within 2 weeks of A-02 infusion;
- CD20 antibody-related treatment must be discontinued within 4 weeks of A-02 infusion or 5 half-lives (whichever is longer);
- CNS disease prophylaxis must be stopped > 1 week prior to A-02 infusion (e.g. intrathecal methotrexate);
- The investigator judged that the subject recovered from the toxicity of the previous anti-tumor treatment to grade 1 or below (except for special grade 2 or below toxicity that cannot be recovered in a short period of time, such as hair loss), suitable for pretreatment. Chemotherapy and treatment of CAR-T cells;
- Women of child-bearing potential and all male subjects must agree to use highly effective methods of contraception for at least 12 months following A-02 infusion and until CAR-T cells are no longer present by PCR on two consecutive tests.
Who cannot join
- Prior treatment with any cell therapy before signing the informed consent form, including CAR-T therapy;
- Subjects with detectable cerebrospinal fluid malignant cells or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
- Subjects with testicular invasion, including those who have had testicular resection;
- Subjects with current or previous history of central nervous system disease, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
- Subjects who have previously received allogeneic hematopoietic stem cell transplantation (HSCT); or suitable and consenting to Autologous hematopoietic stem cell transplantation (ASCT);
- Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of A-02 infusion;
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- Patients on oral anticoagulation therapy within 1 week of A-02 infusion;
- Prior radiation therapy within 2 weeks of A-02 infusion;
- Investigational medicinal product within the last 30 days prior to sign the informed consent form;
- Subjects with active hepatitis B（defined as hepatitis B surface antigen positive, or hepatitis B core antibody positive with hepatitis B virus DNA detection value > 1000 copies/ml）or hepatitis C (HCV RNA positive)
- Subjects positive for HIV antibody or treponema pallidum antibody;
- Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to A-02 infusion)
- Unstable angina and/or myocardial infarction within 6 months prior to sign the informed consent form;
- Previous or concurrent malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to sign the informed consent form);
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to sign the informed consent form;
- A primary malignancy which has been completely resected and in complete remission for ≥ 5 years;
- Pregnant or nursing women (women of childbearing age were tested positive for pregnancy during screening period);
- Cardiac arrhythmia not controlled with medical management;
- Subjects with active neurological auto immune or inflammatory disorders (e.g. Guillain Barre Syndrome, Amyotrophic Lateral Sclerosis);
- Other conditions that the investigator thinks he/she should not be included in this clinical trial, such as poor compliance.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Jianda Hu, Prof., 86-13959169016, drjiandahu@163.com
Ting Yang, Prof., 86-13950210357, yang.hopeting@gmail.com
About this study
Official title: A Single-arm, Open-label, Dose Escalation Study to Explore Safety, Efficacy and Pharmacokinetics of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells in Adult Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma
This is a single-arm, open-label, dose escalation, phase I study, aiming to evaluate the safety and efficacy of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific Chimeric Antigen Receptor (CAR) T-cells in patient with relapsed or refractory diffuse B cell lymphoma.
Read the detailed description
CD19 CAR-T cell therapy has made breakthroughs in the treatment of B cell lymphoma and leukemia, but 30% of patients still have antigen escape, which may be related to variants in tumor cells and the expansion of CD19-negative tumor cells after treatment with CD19 CAR-T cells. CD19/CD20 bispecific CAR-T cell targeting multiple antigens can attack tumor cells while overcoming tumor antigen escape caused by a single target, maximizing efficacy and duration of treatment, and can also solve the problem of uneven distribution or low expression of single target on the tumor surface.
- Being tested
- Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T CellsBiological
Humanized anti-CD19 and CD20 bispecific autologous CAR-T cells injection: the first dose is 1.0×106 /kg, the second dose is 3.0×106 /kg, and the third dose is 8.0×106 /kg. Patients will receive lymphodepleting chemotherapy at least 1 week before CAR-T cell infusion.
| Study group | Role | What they receive |
|---|---|---|
| Humanized anti-CD19 and anti-CD20 dual specific CAR-T cells | Experimental | Not described Receives: Biological: Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The types and Incidence of adverse events
Measured: Up to 12 months
Secondary outcomes (3)
Overall response rate
including CR and PR
Measured: Up to 12 months
Progression-free survival (PFS)
Measured: Up to 12 months
Response duration
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study startDec 2019 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 PositiveStudies of the same condition, open and under way.
- More trials run by Fujian Medical UniversityThe sponsor's other registered studies.
- 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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianda Hu, Fujian Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04215016
- Sponsor's protocol ID
- CART-19-05
- Acronym
- A-02
- Status last verified
- Dec 2019
- First submitted
- 29 Dec 2019
- Last updated
- 2 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label, Dose Escalation Study to Explore Safety, Efficacy and Pharmacokinetics of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells in Adult Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma
- ClinicalTrials.gov ID
- NCT04215016
- Acronym / sponsor ID
- A-02 / CART-19-05
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Fujian Medical UniversityUniversity, hospital or other
- Study start
- Dec 2019 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 2 Jan 2020 (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 single-arm, open-label, dose escalation, phase I study, aiming to evaluate the safety and efficacy of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific Chimeric Antigen Receptor (CAR) T-cells in patient with relapsed or refractory diffuse B cell lymphoma.
Detailed description
CD19 CAR-T cell therapy has made breakthroughs in the treatment of B cell lymphoma and leukemia, but 30% of patients still have antigen escape, which may be related to variants in tumor cells and the expansion of CD19-negative tumor cells after treatment with CD19 CAR-T cells. CD19/CD20 bispecific CAR-T cell targeting multiple antigens can attack tumor cells while overcoming tumor antigen escape caused by a single target, maximizing efficacy and duration of treatment, and can also solve the problem of uneven distribution or low expression of single target on the tumor surface.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Humanized anti-CD19 and anti-CD20 dual specific CAR-T cells | Experimental | Biological: Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- The subject or her/his legally guardian(s) must sign the informed consent form approved by the Institutional Ethics Committee (IEC) prior to any screening procedures;
- Subjects aged 18 years or older with relapsed or refractory DLBCL (primary mediastinal large B-cell lymphoma and transformed follicular lymphoma included), of which refractory is defined as:
- Subjects who have previously received ≥2 lines treatment, and at least including:
- Confirmation for either CD19 or CD20 positivity using immunohistochemistry or flow cytometry;
- According to the initial evaluation, staging and response assessment of Hodgkin's and non-Hodgkin's lymphoma -the Lugano Classification (2014), there is at least one measurable lesion at baseline;
Key exclusion criteria (21 listed)
- Prior treatment with any cell therapy before signing the informed consent form, including CAR-T therapy;
- Subjects with detectable cerebrospinal fluid malignant cells or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
- Subjects with testicular invasion, including those who have had testicular resection;
- Subjects with current or previous history of central nervous system disease, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
- Subjects who have previously received allogeneic hematopoietic stem cell transplantation (HSCT); or suitable and consenting to Autologous hematopoietic stem cell transplantation (ASCT);
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 |
|---|---|---|
| Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T CellsHumanized anti-CD19 and CD20 bispecific autologous CAR-T cells injection: the first dose is 1.0×106 /kg, the second dose is 3.0×106 /kg, and the third dose is 8.0×106 /kg. Patients will receive lymphodepleting chemotherapy at least 1 week before CAR-T cell infusion. | Biological | Humanized anti-CD19 and anti-CD20 dual specific CAR-T cells |
Primary outcome
The types and Incidence of adverse events
Time frame: Up to 12 months
3 secondary outcomes
Overall response rate
Time frame: Up to 12 months
Progression-free survival (PFS)
Time frame: Up to 12 months
Response duration
Time frame: Up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2020.
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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells in people with Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive, run by Fujian Medical 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 39 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: status not confirmed, as of the sponsor's last update on 2 Jan 2020. 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 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 Jianda Hu, Prof.M.D.Ph.D (86-13959169016, drjiandahu@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The types and Incidence of adverse events (time frame: Up to 12 months). 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 2 Jan 2020; AzTrials last refreshed its copy on 8 Nov 2026.