Clinical Trials /

A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL

NCT04595162

Description:

The study is an early, open, single-centered trial. The aim of this study is to evaluate the safety and tolerance of GC019F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 6-12 subjects to receive GC019F therapy.

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

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
  • Official Title: A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: PGC0005
  • NCT ID: NCT04595162

Conditions

  • B-cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
GC019FCAR-T treatment group

Purpose

The study is an early, open, single-centered trial. The aim of this study is to evaluate the safety and tolerance of GC019F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 6-12 subjects to receive GC019F therapy.

Detailed Description

      This study is an early, open, single-centered trial. The major aim of this study is to
      evaluate the safety and tolerance of GC019F CAR-T cell immunotherapy in relapsed or
      refractory B-ALL. The study will include 6-12 subjects to receive GC019F single infusion.
    

Trial Arms

NameTypeDescriptionInterventions
CAR-T treatment groupExperimentalThe patients will receive one dose of GC019F.
  • GC019F

Eligibility Criteria

        Inclusion Criteria:

          1. Aged 18-70 years;

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

          3. Life expectancy≥12 weeks;

          4. CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow
             cytometry;

          5. Relapsed or refractory B- ALL: a) Refractory B- ALL: Fail to achieve a CR after 2
             cycles of a standard induction chemotherapy regimen or one-line/multi-line salvage
             chemotherapy; b) Relapsed B- ALL: Relapse after remission for the first time in 12
             months or relapse after one-line/multi-line salvage chemotherapy; Relapse is defined
             as recurrence of primitive cell in peripheral blood or bone marrow(>5%) after
             remission; c)Relapse after autologous stem cell transplantation or allogeneic
             hematopoietic stem cell transplantation; d)Patients with Philadelphia chromosome
             positive(Ph+) ALL were eligible if they were intolerant to or had failed two lines of
             tyrosine kinase inhibitor (TKI) therapy, or had t315i mutation.

          6. Did not receive hematopoietic stem cell transplantation≤6 months prior to enrollment;

          7. Adequate organ function defined as: a) Creatinine clearance (as estimated by Cockcroft
             Gault method) >60 mL/min; b) Serum ALT/AST <2.5 ULN; c) Total bilirubin <1.5 ULN
             (subjects with Gilbert's syndrome≤3 ULN); d) Cardiac ejection fraction≥50%, no
             evidence of clinically significant pericardial effusion as determined by an ECHO; e)
             No clinically significant pleural effusion; f) Baseline oxygen saturation >92% on room
             air;

          8. Females of reproductive age must be in non-lactation period. Females of childbearing
             potential must have a negative serum or urine pregnancy test. All subjects must use
             medical-approved-contraception (such as intrauterine device and contraceptive drugs)
             during the treatment and in 2 years after cell transfusion treatment; Males should
             avoid sperm donation;

          9. Venous access can be established, peripheral blood mononuclear cells (PBMC) can be
             collected in researcher's judgement;

         10. The subject agrees to and sign informed consent form;

         11. The subject can communicate well with the researcher, is willing and able to comply
             with the research plans, and finish the research according to the research rule.

        Exclusion Criteria:

          1. Isolated extramedullary leukemia or isolated extramedullary disease relapse;

          2. Central nervous system leukemia involved CNS3;

          3. Concomitant malignancy other than cured non-melanoma skin cancer or cervical carcinoma
             in situ or localized prostate cancer or superficial bladder cancer or ductal carcinoma
             in situ or diagnosis of other malignancy exceeds 5 years without relapse or treatment
             during the 5 years;

          4. Any result of the following infectious disease tests is positive: HIV; HCV; HBsAg; or
             HBcAb positive with HBV DNA copies positive; TPPA;

          5. Live vaccine ≤4 weeks prior to enrollment;

          6. For Ph+ ALL, TKI therapy ≤1 week prior to enrollment;

          7. History of anti-CD19 therapy or CAR-T or other gene-editing T cell therapy;

          8. Presence of ≥ grade 2 acute graft-versus-host disease (GVHD, Glucksberg criteria) or
             extensive chronic GVHD (Seattle criteria) that require treatment ≤4 weeks prior to
             enrollment, or during the study period the subject is required to receive anti-GCHD
             therapy in researcher's judgement;

          9. Presence of concomitant disease that require systemic steroids or other immune
             suppressive therapy during the study period in researcher's judgement; Allogeneic cell
             therapy (such as donor lymphocyte infusion, DLI) ≤4 weeks prior to enrollment;

         10. CNS stereotactic radiotherapy ≤4 weeks prior to enrollment;

         11. Toxicities related to previous therapy did not relieved to ≤1 grade, except
             hematological toxicity and alopecia;

         12. Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or
             presence of other intolerant conditions, or severe allergic constitution;

         13. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogren
             syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel
             disease, Hashimoto's thyroiditis, hypothyroidism which can be controlled by thyroid
             hormone replacement therapy is an exception);

         14. For patients that underwent or plan to undergo major surgical operation before CAR-T
             treatment, major surgery which required general anesthesia happened ≤4 weeks prior to
             enrollment, or did not be fully recovered and clinically stable prior to enrollment,
             or be anticipated to undergo major surgical operation which requires general
             anesthesia during the study;

         15. Took drug from other research≤28 days prior to enrollment;

         16. Any unstable cardiovascular diseases happened ≤6 months prior to enrollment, including
             but not limited to, unstable angina, myocardial infarction, heart failure (NYHA grade≥
             III grade), severe arrhythmia that require drug interference, cardiac
             angioplasty/coronary stent implantation/ cardiac bypass surgery ≤6 months prior to
             enrollment;

         17. Presence of central nervous system (CNS) disease or disease history, including
             epilepsy, cerebral ischemia/bleeding, dementia, cerebellar disease, or any autoimmune
             diseases that involve CNS;

         18. Any other condition that researcher think it is inappropriate for the subject to
             anticipate the trial.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events(AE)
Time Frame:15 years
Safety Issue:
Description:AEs will be collected and graded according to ASTCT consensus(for Cytokine Release Syndrome, CRS and Immune Effector Cell-Associated Neurotoxicity Syndrome, ICANS) and CTCAE v5.0(for AE except for CRS/ICANS )

Secondary Outcome Measures

Measure:CAR copies and concentration of GC007F in peripheral blood, bone marrow and CSF
Time Frame:2 years
Safety Issue:
Description:GC007F CAR copies and cells in peripheral blood, bone marrow and CSF will be measured by qPCR and FCM in 2 years
Measure:Overall response rate (ORR) and minimal residual disease negative (MRD-) rate of patients who received GC007F infusion
Time Frame:2 years
Safety Issue:
Description:ORR will be estimated as the percentage of patients who achieved CR or CRi. MRD- rate will be estimated as the percentage of patients who achieved MRD-(blast cells in bone marrow<10^-4 as determined by FCM).
Measure:Duration of response (DOR), progression-free survival (PFS), overall survival (OS) of patients who received GC007F infusion
Time Frame:15 years
Safety Issue:
Description:DOR refers to the time interval from the date when the patient was evaluated as CR/CRi for the first time to the date when the patient was evaluated as disease relapse or death due to any reason. PFS refers to the time interval from the date of GC007F infusion to the date when the patient was evaluated as disease relapse or death due to any reason. OS refers to the time interval from the date of GC007F infusion to the date when the patient died due to any reason.
Measure:Concentration of anti-GC007F antibody after infusion
Time Frame:2 years
Safety Issue:
Description:After GC007F infusion, GC007F antibody in peripheral blood will be measured in 2 years

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peking University Third Hospital

Last Updated

October 14, 2020