B-cell Lymphoma RefractoryEarly Phase 1NCT04303247
CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL
A Early Phase 1 study testing CD19 and CD22 targeted CAR-T cells in people with B-cell Lymphoma Refractory and B-cell Lymphoma Recurrent, run by Xinqiao Hospital of Chongqing at 1 site in China.
Trial summary
Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies. There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- B-cell Lymphoma Refractory, B-cell Lymphoma Recurrent
- What is being tested?
- CD19 and CD22 targeted CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2020to 1 May 2023
- Phase
- Early 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet the following criteria for inclusion in the study： 1) Male or female subjects between the ages of 18 and 75（including critical values）； 2) Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
- a） Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
- b） Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved complete remission after standard systematic treatment and second-line treatment. Or the disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell transplantation (not limited to the previous therapeutic regimen) ； c） Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline； d） Subjects with TFL must receive chemotherapyInclusion criteria： Subjects must meet the following criteria for inclusion in the study：
- Male or female subjects between the ages of 18 and 75（including critical values）；
- Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
- Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
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- Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved complete remission after standard systematic treatment and second-line treatment. Or the disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell transplantation (not limited to the previous therapeutic regimen) ；
- Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline；
- Subjects with TFL must receive chemotherapy before transformation and meet the above definition of relapse or refractory after transformation.
- According to Lugano response criteria 2014, there should be at least one evaluable tumor focus: the longest diameter of intranodal focus > 1.5cm, the longest diameter of extranodal focus > 1.0cm；
- Positive expression of CD19 or CD22 in tumor tissue；
- Subjects who have no effect or relapse after single-target CAR-T treatment can also be included in the group.
- Approved anti-tumor therapies, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 2 weeks before the precondition.
- ECOG≤1；
- Life expectancy ≥ 3 months；
- Neutrophil absolute count ≥ 1×10^9/L；
- platelet count ≥ 50×10^9/L；
- Absolute lymphocyte count ≥ 1×10^8/L ；
- Adequate organ function reserve :
- GPT, GST ≤ 2.5× UNL（upper normal limit）；
- Creatinine clearance (Cockcroft Gault method）≥60mL/min；
- Serum total bilirubin ≤1.5× UNL；
- The left ventricular ejection fraction (LVEF) ≥ 50% was diagnosed by echocardiography, and there was no clinically significant pericardial effusion and ECG abnormality；
- Basic oxygen saturation in indoor natural air environment > 92%；
- It can establish the venous access needed for collection without the contraindications of leukocyte collection；
- For female subjects of childbearing age, results are negative in urine pregnancy test before screening and administration, and subjects agree to take effective contraceptive measures at least one year after infusion; Male subjects with partners' fertility must agree to use effective barrier contraceptive methods at least one year after infusion, and avoid sperm donation；
- Voluntary signing of informed consent;
Who cannot join
- Any of the following points shall be deemed as no entry into this study：
- Other tumors except cured non-melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with complete remission of more than 5 years)；
- Severe mental disorders；
- A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
- History of allogeneic stem cell transplantation；
- Heart disease with grade III-IV heart failure [NYHA classification], myocardial infarction, angioplasty or stenting, unstable angina or other heart diseases with prominent clinical symptoms within one year before admission；
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- Subjects with any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, bile drainage tube or pleura/peritoneum/pericardium catheter), should be excluded. (Special central venous catheter is allowed)；
- Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
- Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
- Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
- Active infection requiring systematic treatment within 2 weeks before single collection；
- Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
- History of autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic lupus erythematosus) that cause end-organ damage or require systemic immunosuppressive medications or systemic disease modifying drugs in the past 2 years；
- Presence of pulmonary fibrosis；
- Subjects who have received other clinical trial treatment within 4 weeks before participating in this trial should be excluded. Or the signing date of informed consent is within 5 half-lives of the last application of another clinical trial (whichever is longer)；
- Subjects with poor compliance due to physiological, family, social, geographical and other factors, or those unable to cooperate with the study plan or follow-up；
- At the discretion of the investigator, there are complications requiring systemic corticosteroid therapy (≥ 5mg / day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive drugs within 6 months after this clinical research treatment；
- The lactating woman who is reluctant to stop breastfeeding；
- Any other condition considered unsuitable by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Hematology, Xinqiao Hospital
Chongqing, Chongqing Municipality, 400037
About this study
Official title: CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL: a Multi-center, Uncontrolled Trial.
Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies. There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. To make further improvement, combining CD19 and CD22 as dual-targets for CAR-T cells, which adapt the FasT CAR-T cells manufacture technology to shorten the manufacture time and maintain the stemness of CAR-T cells. We launch such a clinical trial using CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B-cell NHL to evaluate the efficacy and safety of CD19 and CD22 targeted CAR-T cell therapy.
- Being tested
- CD19 and CD22 targeted CAR-T cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 and CD22 targeted CAR-T cellsBiological
The T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma.
| Study group | Role | What they receive |
|---|---|---|
| CD19+CD22 targeted CAR-T | Experimental | The study will employ dose level cohorts of three patients that will be treated at each level described below, based on the number of T cells to be infused using the "3 + 3" dose-escalation strategy to find MTD followed by a dose-expansion phase at determined optimal dosage.
dosage: the number of anti CD19+CD22 CAR T cells
-1(if needed) 1×10^5/KG
1. 3×10^5 /KG
2. 6×10^5 /KG
3. 1×10^6/KG
Treatment follows a lymphodepletion, chemotherapy regimen that consists of Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) for 3 days prior to cell infusion. Receives: Biological: CD19 and CD22 targeted CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells
ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value
Measured: 4 weeks after infusion
The safey evaluation of CD19 and CD22 targeted CAR-T cells
the appearence of dosage limited toxicity
Measured: within 4 weeks after infusion
Secondary outcomes (1)
The long-term efficiency of CD19 and CD22 targeted CAR-T cells
ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value
Measured: up to 2 years after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start1 May 2020 (estimated)
- Primary completion1 May 2021 (estimated)
- Study completion1 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Lymphoma RefractoryStudies 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
- Early 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
- Xinqiao Hospital of Chongqing
- Sponsor type
- University, hospital or other
- Collaborators
- Gracell Biotechnologies (Shanghai) Co., Ltd., 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, The Affiliated Hospital Of Guizhou Medical University, Tang-Du Hospital, The General Hospital of Western Theater Command, Chongqing University Cancer Hospital
- Responsible party
- Principal investigator, Xi Zhang, MD, Xinqiao Hospital of Chongqing
- Investigators
- Xi Zhang, MD phD, Principal investigator, Xinqiao Hospital of Chongqing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04303247
- Sponsor's protocol ID
- dual CD19/CD22 CAR-T
- Status last verified
- Mar 2020
- First submitted
- 5 Mar 2020
- Last updated
- 11 Mar 2020
- 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 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL: a Multi-center, Uncontrolled Trial.
- ClinicalTrials.gov ID
- NCT04303247
- Acronym / sponsor ID
- dual CD19/CD22 CAR-T
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xinqiao Hospital of ChongqingUniversity, hospital or other
- Collaborators
- Gracell Biotechnologies (Shanghai) Co., Ltd., 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China, The Affiliated Hospital Of Guizhou Medical University, Tang-Du Hospital, The General Hospital of Western Theater Command, Chongqing University Cancer Hospital
- Study start
- 1 May 2020 (estimated)
- Primary completion
- 1 May 2021 (estimated)
- Study completion
- 1 May 2023 (estimated)
- First posted
- 11 Mar 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.
Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies. There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. To make further improvement, combining CD19 and CD22 as dual-targets for CAR-T cells, which adapt the FasT CAR-T cells manufacture technology to shorten the manufacture time and maintain the stemness of CAR-T cells. We launch such a clinical trial using CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B-cell NHL to evaluate the efficacy and safety of CD19 and CD22 targeted CAR-T cell therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19+CD22 targeted CAR-T | Experimental | Biological: CD19 and CD22 targeted CAR-T cellsThe study will employ dose level cohorts of three patients that will be treated at each level described below, based on the number of T cells to be infused using the "3 + 3" dose-escalation strategy to find MTD followed by a dose-expansion phase at determined optimal dosage. dosage: the number of anti CD19+CD22 CAR T cells -1(if needed) 1×10^5/KG 1. 3×10^5 /KG 2. 6×10^5 /KG 3. 1×10^6/KG Treatment follows a lymphodepletion, chemotherapy regimen that consists of Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) for 3 days prior to cell infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Subjects must meet the following criteria for inclusion in the study： 1) Male or female subjects between the ages of 18 and 75（including critical values）； 2) Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
- a） Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
- b） Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved complete remission after standard systematic treatment and second-line treatment. Or the disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell transplantation (not limited to the previous therapeutic regimen) ； c） Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline； d） Subjects with TFL must receive chemotherapyInclusion criteria： Subjects must meet the following criteria for inclusion in the study：
- Male or female subjects between the ages of 18 and 75（including critical values）；
- Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
Key exclusion criteria (19 listed)
- Any of the following points shall be deemed as no entry into this study：
- Other tumors except cured non-melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with complete remission of more than 5 years)；
- Severe mental disorders；
- A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
- History of allogeneic stem cell transplantation；
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 |
|---|---|---|
| CD19 and CD22 targeted CAR-T cellsThe T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma. | Biological | CD19+CD22 targeted CAR-T |
Primary outcome
The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells
Time frame: 4 weeks after infusion
ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value
The safey evaluation of CD19 and CD22 targeted CAR-T cells
Time frame: within 4 weeks after infusion
the appearence of dosage limited toxicity
1 secondary outcome
The long-term efficiency of CD19 and CD22 targeted CAR-T cells
Time frame: up to 2 years after infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
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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.
Xi Zhang, MD phD principal investigator
Xinqiao Hospital of Chongqing
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing CD19 and CD22 targeted CAR-T cells in people with B-cell Lymphoma Refractory and B-cell Lymphoma Recurrent, run by Xinqiao Hospital of Chongqing 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 27 inclusion and 19 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 11 Mar 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Xi Zhang, MD phD (13808310064 ext. +86, zhangxxi@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells (time frame: 4 weeks after infusion). 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?
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 11 Mar 2020.