- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04303247
CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL
CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL: a Multi-center, Uncontrolled Trial.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Chongqing
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ChongQing, Chongqing, China, 400037
- Department of Hematology, Xinqiao Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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.
- 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;
Exclusion Criteria:
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;
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: CD19+CD22 targeted CAR-T
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
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. |
The T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells
Time Frame: 4 weeks after infusion
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ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value
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4 weeks after infusion
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The safey evaluation of CD19 and CD22 targeted CAR-T cells
Time Frame: within 4 weeks after infusion
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the appearence of dosage limited toxicity
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within 4 weeks after infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The long-term efficiency of CD19 and CD22 targeted CAR-T cells
Time Frame: up to 2 years after infusion
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ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value
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up to 2 years after infusion
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Xi Zhang, MD phD, Xinqiao Hospital of Chongqing
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- dual CD19/CD22 CAR-T
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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