Clinical Trials /

CD19-CD22 Chimeric Antigen Receptor T (CAR-T) Cell for Treatment of B Cell Acute Lymphoblastic Leukemia (B-ALL)

NCT04034446

Description:

This is a single arm, open-label, single center study to determine the safety and efficacy of CD19-CD22 CAR-T cells in patients with CD19+CD22+ Leukemia.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD19-CD22 Chimeric Antigen Receptor T (CAR-T) Cell for Treatment of B Cell Acute Lymphoblastic Leukemia (B-ALL)
  • Official Title: a Feasibility and Safety Study of Bispecific CD19-CD22 CAR-T Cell in the Treatment of Relapsed or Refractory B-ALL

Clinical Trial IDs

  • ORG STUDY ID: HY004001
  • NCT ID: NCT04034446

Conditions

  • Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
CD19-CD22 CAR-T cellsA

Purpose

This is a single arm, open-label, single center study to determine the safety and efficacy of CD19-CD22 CAR-T cells in patients with CD19+CD22+ Leukemia.

Detailed Description

      This is a single arm, open-label, single center study to determine the safety and efficacy of
      CD19-CD22 CAR-T cells in patients with relapsed or refractory B-ALL. The study will have the
      following sequential phases: Screening, Pre-Treatment (Cell Product Preparation &
      Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total
      duration of the study is 2 years from CD19-CD22 CAR-T cell infusion.
    

Trial Arms

NameTypeDescriptionInterventions
AExperimentalSingle dose of CD19-CD22 CAR-T cells
  • CD19-CD22 CAR-T cells

Eligibility Criteria

        Inclusion Criteria:

          1. Informed consent is signed by a subject or his lineal relation.

          2. Age 3 and older.

          3. Documentation of cluster of differentiation 19 (CD19) and or cluster of
             differentiation 19 (CD22) expression on leukemic blasts in the BM, peripheral blood
             within 3 months of screening.;

          4. Relapsed or refractory B-cell ALL

               -  Relapse within 12 months of first remission

               -  Without remission after 2 cycles of induction chemotherapy regimen.

               -  Without remission or relapse after salvage treatments.

               -  Any BM relapse after autologous stem cell transplantation (ASCT).

          5. Without remission or relapse after any prior CD19 targeted therapy;

          6. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
             intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI); no
             TKI salvage treatments if the patient has a BCR-ABL1 kinase domain gatekeeper mutation
             Thr315Ile (T315I) mutation.

          7. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening;

          8. Eastern cooperative oncology group (ECOG) performance status of 0 to 2.

          9. Adequate organ function defined as:

               -  Aspartate aminotransferase (AST) ≤3 upper limit of normal (ULN);

               -  Serum alanine aminotransferase (ALT) ≤3 ULN;

               -  Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome;

               -  Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct
                  bilirubin ≤ 1.5 ULN will be eligible.

               -  A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min(Cockcroft and
                  Gault)

               -  Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen
                  saturation > 91% on room air.

               -  Absolute lymphocyte count ≥0.3 x 10⁹/L.

         10. Women of child-bearing potential and all male participants must use highly effective
             methods of contraception for a period of 1 year after the CD19-CD22 CAR-T cells
             infusion.

        Exclusion Criteria:

          1. Active central nervous system leukemia

          2. Patients with evidence of currently uncontrollable serious active infections (e.g.,
             sepsis, bacteremia, fungemia, viremia, etc.).

          3. Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface
             antigen (HBsAg) and hepatitis C virus (HCV) antibody.

          4. Major surgery within ≤ 4 weeks before enrollment.

          5. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
             intent.

          6. Impaired cardiac function:

               -  Left Ventricular Ejection Fraction (LVEF) ≤45%;

               -  III/IV congestive heart failure (NYHA);

               -  Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular
                  tachycardia);

               -  Corrected QT interval (QTc) ≥450ms (male) or QTc≥470ms (female)(QTc using
                  Bazett's formula (QTcB)=QT/RR^0.5);

               -  Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent
                  surgery.

               -  Other heart diseases that have been judged by the investigator to be unsuitable
                  for receiving cell therapy.

          7. Patients with a history of epilepsy or other active central nervous system diseases.

          8. Life expectancy < 12 weeks.

          9. Allergy to macromolecule biopharmaceuticals such as antibodies or cytokines.

         10. Subjects who are receiving systemic steroid treatment and who have been determined by
             the researchers to require long-term treatment with systemic steroids during
             treatment, and subjects treated with systemic steroids must be excluded < 72 hours
             prior to CNCT19 infusion (except inhalation or local use).

         11. Patients with other conditions making the patients unsuitable for receiving cell
             therapy as judged by the investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Response at Day 28 days
Time Frame:1 month
Safety Issue:
Description:
Measure:Percentage of patients who achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at month 6 without SCT between CD19-CD22 CAR-T cells infusion and Month 6 response assessment.
Time Frame:6 months
Safety Issue:
Description:
Measure:Percentage of patients who achieve CR or CRi with minimal residual disease (MRD) negative bone marrow
Time Frame:6 months
Safety Issue:
Description:
Measure:Relapse-free survival (RFS)
Time Frame:24 months
Safety Issue:
Description:
Measure:Duration of remission (DOR)
Time Frame:24 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institute of Hematology & Blood Diseases Hospital

Trial Keywords

  • Relapsed
  • Refractory
  • B-ALL

Last Updated