Diffuse Large B Cell LymphomaPhase 1NCT04486872
An Exploratory Clinical Trial of Autologous Humanized Anti-cluster of Differentiation Antigen 19/20(CD19/CD20) Dual Specific CAR-T Cells Injection
A Phase 1 study testing Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells in people with Diffuse Large B Cell Lymphoma, run by First Affiliated Hospital of Zhejiang 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
- Diffuse Large B Cell Lymphoma
- 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
- 25 Jul 2020to 25 Jun 2022
- 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 (including primary mediastinal large B-cell lymphoma and transformed follicular lymphoma), 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(accepting the previous results from the a third-level grade A hospitals before the collection of peripheral blood mononuclear cells or peripheral blood. For CD20 positive only, the investigator needs to determine whether the treatment benefit);
- According to the preliminary assessment of Hodgkin's lymphoma and non-Hodgkin's lymphoma, staging and response assessment recommendations (2014 version), there is at least one measurable lesion at baseline;
- If the subject has received a single target in the past, such as CD19-CAR cell therapy, it must be confirmed that the disease has progressed or relapsed after treatment and is at least 1 month from the planned single collection period
- 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；[eGFR=186×（age）-0.203×SCr-1.154（mg/dl）， female ×0.742 on the basis of the calculation results]；
- Liver function defined as:
- Alanine aminotransferase (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;
- 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/m2/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 Polymerase chain reaction(PCR) on two consecutive tests.
Who cannot join
- Subjects who meet any of the following criteria will not be enrolled:
- Subjects who have received any CD19/CD20 dual-target cell therapy products before signing the informed consent form;
- 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 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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- 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);
- 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
First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310009
Jie Jin, Prof, 13505716779, jiej0503@163.com
Jianzhong Shentu, Prof, 13957111817, stjz@zju.edu.cn
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.
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- Autologous humanized anti-CD19 and anti-CD20 dual specific CAR-T Cells
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
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
Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells injection. Within 3 to 5 days after the pretreatment, the subjects received a single A-02 reinfusion, the infusion dose of each group of subjects 1.00 × 10^6/kg, 3.00 × 10^6/kg or 5.00 × 10^6/kg (if applicable), it is recommended to complete the infusion within 30 min after cell recovery.
| Study group | Role | What they receive |
|---|---|---|
| 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
Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
Measured: Up to 12 months
Secondary outcomes (5)
Duration of overall response
Time from the first occurrence of CR (complete response) or PR (partial response) to the first diagnosis of PD (progressive disease)or recurrence.
Measured: Up to 12 months
Overall survival
Time from randomization to death due to any cause
Measured: Up to 12 months
Progression-free survival
Time from enrollment to tumor progression or death.
Measured: Up to 12 months
Objective response rate
The proportion of CR (complete response) and PR (partial response).
Measured: Up to 12 months
Duration of response
Duration of response is defined as the time from the date of first occurrence of CR (complete response) or PR (partial response) to the date of the first documented PD (progressive disease) or death due to any cause.
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 posted27 Jul 2020
- Study start25 Jul 2020
- Primary completion11 May 2022 (estimated)
- Study completion25 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang 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
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, shentu jianzhong, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486872
- Sponsor's protocol ID
- A-02 POC-01
- Status last verified
- Aug 2020
- First submitted
- 17 Jul 2020
- Last updated
- 26 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 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
- NCT04486872
- Acronym / sponsor ID
- A-02 POC-01
- Conditions
- Diffuse Large B Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 25 Jul 2020 (actual)
- Primary completion
- 11 May 2022 (estimated)
- Study completion
- 25 Jun 2022 (estimated)
- First posted
- 27 Jul 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 |
|---|---|---|
| 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 (including primary mediastinal large B-cell lymphoma and transformed follicular lymphoma), 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(accepting the previous results from the a third-level grade A hospitals before the collection of peripheral blood mononuclear cells or peripheral blood. For CD20 positive only, the investigator needs to determine whether the treatment benefit);
- According to the preliminary assessment of Hodgkin's lymphoma and non-Hodgkin's lymphoma, staging and response assessment recommendations (2014 version), there is at least one measurable lesion at baseline;
Key exclusion criteria (18 listed)
- Subjects who have received any CD19/CD20 dual-target cell therapy products before signing the informed consent form;
- 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 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;
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 CellsAutologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells injection. Within 3 to 5 days after the pretreatment, the subjects received a single A-02 reinfusion, the infusion dose of each group of subjects 1.00 × 10^6/kg, 3.00 × 10^6/kg or 5.00 × 10^6/kg (if applicable), it is recommended to complete the infusion within 30 min after cell recovery. | Biological | 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
Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
5 secondary outcomes
Duration of overall response
Time frame: Up to 12 months
Overall survival
Time frame: Up to 12 months
Progression-free survival
Time frame: Up to 12 months
Objective response rate
Time frame: Up to 12 months
Duration of response
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 26 Aug 2020.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Individual participant dataSharing planned: No
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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. 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 Diffuse Large B Cell Lymphoma, run by First Affiliated Hospital of Zhejiang 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 18 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 26 Aug 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 Jie Jin, Prof (13505716779, jiej0503@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?
On the ClinicalTrials.gov record for NCT04486872, 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 26 Aug 2020.