Clinical Trials /

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

NCT04412174

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-NHL. The investigators plan to include 18 subjects to receive GC022F therapy.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: PGC011
  • NCT ID: NCT04412174

Conditions

  • B-cell Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
GC022FGC022F

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-NHL. The investigators plan to include 18 subjects to receive GC022F therapy.

Trial Arms

NameTypeDescriptionInterventions
GC022FExperimentalThe patients will receive GC022F CAR-T treatment. GC022F dosage ranges from 3×10^5 to 1×10^6 CAR+T/Kg.
  • GC022F

Eligibility Criteria

        Inclusion Criteria:

          1. Aged 18-70 years;

          2. Relapsed or refractory B cell non-Hodgkin's lymphoma (B-NHL): 1)
             Chemotherapy-refractory disease, defined as one or more of the following: a) No
             response to first-line therapy (primary refractory disease, subjects who are
             intolerant to first-line therapy chemotherapy are excluded): i. PD as the best
             response to first-line therapy; ii.SD as the best response after at least 4 cycles of
             first-line therapy (e.g., 4 cycles of R-CHOP) with SD duration no longer than 6 months
             from last dose of therapy; b) No response to second or greater lines of therapy: i. PD
             as the best response to most recent therapy regimen; ii. SD as the best response after
             at least 2 cycles of last line of therapy with SD duration no longer than 6 months
             from last dose of therapy; c) Refractory post-ASCT(autologous stem cell
             transplantation): i. Disease progression or relapsed ≤12 months of ASCT (must have
             biopsy proven recurrence in relapsed subjects); ii. If salvage therapy is given
             post-ASCT, the subject must have had no response to or relapsed after the last line of
             therapy; d) PD or SD as the best response after previous CAR-T therapy (at least 3
             months ago); 2) Subjects must have received adequate prior therapy including at a
             minimum: anti-CD20 monoclonal antibody unless investigator determines that tumor is
             CD20 negative, and an anthracycline containing chemotherapy regimen; for subjects with
             transformed FL must have received prior chemotherapy for follicular lymphoma and
             subsequently have chemotherapy-refractory disease after transformation to DLBCL; 3) At
             least 1 measurable lesion according to the Lugano Response Criteria (Cheson 2014).
             Lesions that have been previously irradiated will be considered measurable only if
             progression has been documented following completion of radiation therapy: a) For
             nodular lesions, longest diameter ≥15mm, no requirement for shortest diameter; b) For
             extranodal lesions (lesions other than lymph node and nodular lesions, including liver
             and spleen), longest diameter ≥10mm, no requirement for shortest diameter;

          3. ECOG performance status ≤2 score;

          4. Life expectancy≥12 weeks;

          5. CD19 and/or CD22 positive expression demonstrated in tumor tissue;

          6. Adequate organ function defined as: 1) Creatinine clearance (as estimated by Cockcroft
             Gault method)>60 mL/min; for male, creatinine clearance=[
             (140-age)×weight(kg)]/[0.818×creatinine (μmol/L)] ; for female, creatinine clearance
             =[(140-age)×weight(kg)×0.85]/[0.818×creatinine (μmol/L)]; 2) Serum ALT/AST<2.5×ULN
             (for subjects with liver metastases, ALT/AST≤5×ULN); 3) Total bilirubin<1.5×ULN (for
             subjects with Gilbert's syndrome, total bilirubin≤ 3×ULN); 4) Left ventricular
             ejection fraction (LVEF)>50%, no evidence of clinically significant pericardial
             effusion as determined by an ECHO; 5) No clinically significant pleural effusion; 6)
             Baseline oxygen saturation >92% on room air;

          7. Females of reproductive age must be in non-lactation period. Females of childbearing
             potential must have a negative hypersensitive serum pregnancy test. All subjects must
             use medical-approved-contraception (such as intrauterine device and contraceptive
             drugs) during the period of treatment and in 2 years after CAR-T infusion; males
             should avoid sperm donation;

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

          9. Agrees to sign informed consent form;

         10. Be able to make good communication with researchers, willing and able to comply with
             the planned visit, complete the research according to regulations.

        Exclusion Criteria:

          1. Gastrointestinal involvement;

          2. Active central nervous system (CNS) involvement;

          3. Concomitant malignancy other than: cured non-melanoma skin cancer, cervical carcinoma
             in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in
             situ, other malignancy whose disease-free survival exceeds 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. Autologous stem cell transplantation (ASCT) ≤6 weeks prior to enrollment, history of
             allogeneic hematopoietic stem cell transplantation (allo-HSCT);

          7. Presence of complication that require systemic corticosteroids or other
             immunosuppressive drugs therapy during the trial in researcher's judgement;

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

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

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

         11. Presence of active autoimmune disease (including but not limited to, 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);

         12. Major surgical operation that require 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 that require general anesthesia
             during the study;

         13. Usage of investigational drug ≤28 days prior to enrollment;

         14. Any unstable cardiovascular disease 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;

         15. Presence of CNS disease or disease history, including epilepsy, cerebral
             Ischemia/bleeding, dementia, cerebellar disease, any autoimmune disease that involves
             CNS;

         16. 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:Type and incidence of DLT, incidence and severity of treatment related AE, CRS and Neurotoxicity (Safety and tolerability)
Time Frame:2 years
Safety Issue:
Description:AE 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:CAR copies of GC022F in peripheral blood, bone marrow, CSF and tumor tissue (amplification and persistence)
Time Frame:2 years
Safety Issue:
Description:GC022F CAR copies in peripheral blood, tumor tissue, bone marrow and CSF will be measured by qPCR in 2 years.
Measure:CAR cells of GC022F in peripheral blood, bone marrow and CSF (amplification and persistence)
Time Frame:2 years
Safety Issue:
Description:GC022F CAR cells in peripheral blood, bone marrow and CSF will be measured by FCM in 2 years.
Measure:Objective response rate (ORR) (efficacy)
Time Frame:3 months
Safety Issue:
Description:ORR will be calculated as the percents of patients who achieved CR or PR.
Measure:Duration of Response (DOR) (efficacy)
Time Frame:2 years
Safety Issue:
Description:DOR will be calculated as the time from the first assessment of CR or PR to the first assessment of relapse or death from any cause.
Measure:Progression-Free Survival (PFS) (efficacy)
Time Frame:2 years
Safety Issue:
Description:PFS will be calculated as the time from CAR-T infusion to disease progression or death from any cause (whichever occurs first).
Measure:Overall Survival (OS) (efficacy)
Time Frame:2 years
Safety Issue:
Description:OS will be calculated as the time from CAR-T infusion to death from any cause.

Details

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

Last Updated

June 1, 2020