Clinical Trials /

A Study of GC022F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL

NCT04129099

Description:

The study is an early, open, single-centered trial. The aim of this study is to evaluate the safety and tolerance of GC022F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 18 subjects to receive GC022F therapy.

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

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of GC022F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
  • Official Title: A Study of GC007F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL

Clinical Trial IDs

  • ORG STUDY ID: PGC0006
  • NCT ID: NCT04129099

Conditions

  • B-cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
GC022FCAR-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 GC022F CAR-T cell immunotherapy in relapsed or refractory B-ALL. The study will include 18 subjects to receive GC022F therapy.

Trial Arms

NameTypeDescriptionInterventions
CAR-T treatment groupExperimentalThe patients will receive one dose of GC022F. GC022F dosage ranges from 6×10^4 to 1.5×10^5 CAR+T/Kg.
  • GC022F

Eligibility Criteria

        Inclusion Criteria:

          1. Aged 2-70 years;

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

          3. Life expectancy≥12 weeks;

          4. CD19 and/or CD22 tumor expression demonstrated in bone marrow or peripheral blood by
             flow cytometry;

          5. Relapsed or refractory B- ALL: a) Refractory B- ALL: MRD≥0.1% or 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 MRD≥0.1% or 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; Relapse is defined as above;
             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) >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 period of trial and in 2 years after cell transfusion therapy; 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, willing and able to comply with
             the planned visit, research, treatment planning, laboratory and other test procedures.

        Exclusion Criteria:

          1. Isolated extra-medullary disease relapse;

          2. Central nervous system leukemia involved CNS-3;

          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 virology 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 weeks prior to enrollment;

          7. 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;

          8. Presence of concomitant disease that require systemic steroids or other immune
             suppressive therapy during the study period in researcher's judgement;

          9. 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, surgical operation 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 during the study;

         15. 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;

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

         17. Presence of active infection that require therapy ≤2 weeks prior to apheresis;

         18. Any other conditions that researcher think it is inappropriate for the subject to
             anticipate the trial.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:GC022F safety and tolerance in human
Time Frame:2 years
Safety Issue:
Description:Adverse events(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 CRS/ICANS )

Secondary Outcome Measures

Measure:GC022F amplification and persistence
Time Frame:2 years
Safety Issue:
Description:GC022F CAR copies and cells in peripheral blood, bone marrow and CSF will be measured by qPCR and FCM in 2 years
Measure:GC022F efficacy
Time Frame:2 years
Safety Issue:
Description:Response rates will be estimated as the percents of patients whose best response is complete remission and MRD negative complete remission.
Measure:GC022F humoral immune response
Time Frame:2 years
Safety Issue:
Description:After GC022F infusion, GC022F antibody in peripheral blood will be measured in 2 years

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hebei Yanda Ludaopei Hospital

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