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CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04303247
Recruitment Status : Not yet recruiting
First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Collaborators:
Gracell Biotechnology 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
Information provided by (Responsible Party):
Xi Zhang, MD, Xinqiao Hospital of Chongqing

Brief 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. 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.

Condition or disease Intervention/treatment Phase
B-cell Lymphoma Refractory B-cell Lymphoma Recurrent Biological: CD19 and CD22 targeted CAR-T cells Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: no masking
Primary Purpose: Treatment
Official Title: CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL: a Multi-center, Uncontrolled Trial.
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : May 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

  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.

Biological: CD19 and CD22 targeted CAR-T cells
The T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma.




Primary Outcome Measures :
  1. 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

  2. The safey evaluation of CD19 and CD22 targeted CAR-T cells [ Time Frame: within 4 weeks after infusion ]
    the appearence of dosage limited toxicity


Secondary Outcome Measures :
  1. The long-term efficiency of CD19 and CD22 targeted CAR-T cells [ Time Frame: up to 2 years after infusion ]
    ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  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) :

    1. 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.
    2. 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) ;
    3. Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline;
    4. Subjects with TFL must receive chemotherapy before transformation and meet the above definition of relapse or refractory after transformation.
  3. 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;
  4. Positive expression of CD19 or CD22 in tumor tissue;
  5. Subjects who have no effect or relapse after single-target CAR-T treatment can also be included in the group.
  6. Approved anti-tumor therapies, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 2 weeks before the precondition.
  7. ECOG≤1;
  8. Life expectancy ≥ 3 months;
  9. Neutrophil absolute count ≥ 1×10^9/L;
  10. platelet count ≥ 50×10^9/L;
  11. Absolute lymphocyte count ≥ 1×10^8/L ;
  12. Adequate organ function reserve :

    1. GPT, GST ≤ 2.5× UNL(upper normal limit);
    2. Creatinine clearance (Cockcroft Gault method)≥60mL/min;
    3. Serum total bilirubin ≤1.5× UNL;
    4. The left ventricular ejection fraction (LVEF) ≥ 50% was diagnosed by echocardiography, and there was no clinically significant pericardial effusion and ECG abnormality;
    5. Basic oxygen saturation in indoor natural air environment > 92%;
  13. It can establish the venous access needed for collection without the contraindications of leukocyte collection;
  14. 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;
  15. Voluntary signing of informed consent;

Exclusion Criteria:

Any of the following points shall be deemed as no entry into this study:

  1. 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);
  2. Severe mental disorders;
  3. A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome;
  4. History of allogeneic stem cell transplantation;
  5. 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;
  6. 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);
  7. Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis;
  8. Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS;
  9. Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg;
  10. Active infection requiring systematic treatment within 2 weeks before single collection;
  11. Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy;
  12. 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;
  13. Presence of pulmonary fibrosis;
  14. 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);
  15. 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;
  16. 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;
  17. The lactating woman who is reluctant to stop breastfeeding;
  18. Any other condition considered unsuitable by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04303247


Contacts
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Contact: Xi Zhang, MD phD 13808310064 ext +86 zhangxxi@sina.com
Contact: Ruihao Huang 18984398751 ext +86 1169731117@qq.com

Locations
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China, Chongqing
Department of Hematology, Xinqiao Hospital
ChongQing, Chongqing, China, 400037
Sponsors and Collaborators
Xinqiao Hospital of Chongqing
Gracell Biotechnology 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
Investigators
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Principal Investigator: Xi Zhang, MD phD Xinqiao Hospital of Chongqing
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Responsible Party: Xi Zhang, MD, Chef of Hematology Department, Xinqiao Hospital of Chongqing
ClinicalTrials.gov Identifier: NCT04303247    
Other Study ID Numbers: dual CD19/CD22 CAR-T
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin