Clinical Trials /

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

NCT04303247

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Mantle Cell Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL
  • Official Title: CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL: a Multi-center, Uncontrolled Trial.

Clinical Trial IDs

  • ORG STUDY ID: dual CD19/CD22 CAR-T
  • NCT ID: NCT04303247

Conditions

  • B-cell Lymphoma Refractory
  • B-cell Lymphoma Recurrent

Interventions

DrugSynonymsArms
CD19 and CD22 targeted CAR-T cellsCD19+CD22 targeted CAR-T

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CD19+CD22 targeted CAR-TExperimentalThe 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 3×10^5 /KG 6×10^5 /KG 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.
  • CD19 and CD22 targeted CAR-T cells

Eligibility 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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The anti-tumor efficiency of CD19 and CD22 targeted CAR-T cells
Time Frame:4 weeks after infusion
Safety Issue:
Description:ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Secondary Outcome Measures

Measure:The long-term efficiency of CD19 and CD22 targeted CAR-T cells
Time Frame:up to 2 years after infusion
Safety Issue:
Description:ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Xinqiao Hospital of Chongqing

Last Updated

March 8, 2020