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A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL

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ClinicalTrials.gov Identifier: NCT03825731
Recruitment Status : Recruiting
First Posted : January 31, 2019
Last Update Posted : January 31, 2019
Sponsor:
Collaborator:
Gracell Biotechnology Ltd.
Information provided by (Responsible Party):
Hebei Yanda Ludaopei Hospital

Tracking Information
First Submitted Date  ICMJE January 22, 2019
First Posted Date  ICMJE January 31, 2019
Last Update Posted Date January 31, 2019
Actual Study Start Date  ICMJE January 17, 2019
Estimated Primary Completion Date September 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
  • Number of Patients with Dose Limiting Toxicity [ Time Frame: 12 weeks ]
    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GC022 cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5
  • Incidence of adverse events [ Time Frame: 12 weeks ]
    After GC022 infusion, adverse events will be graded as CTCAE 4.0
  • GC022 persistence [ Time Frame: 12 weeks ]
    After GC022 infusion, GC022 CAR copies in peripheral blood. bone marrow and CSF will be measured by qPCR in 12 weeks
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
Percents of Patients with best response as complete remission and MRD negative complete remission [ Time Frame: 12 weeks ]
Response rates will be estimated as the percents of patients whose best response is complete remission and MRD negative complete remission
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
Official Title  ICMJE A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
Brief Summary The study is an early, open, single-centered trial. The aim of this study is to evaluate the safety and tolerance of GC022 CAR-T cell immunotherapy in relapsed or refractory B-ALL. The investigators plan to include 20 subjects to receive GC022 therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Acute Lymphoblastic Leukemia
Intervention  ICMJE Biological: GC022
GC022 is a bispecific CAR-T cell immunotherapy that targeted CD19 and CD22. The subjects will receive one dose of GC022 infusion. The dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.
Study Arms  ICMJE Experimental: GC022
The patients will receive GC022 CAR-T treatment. GC022 dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.
Intervention: Biological: GC022
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 30, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 16, 2019
Estimated Primary Completion Date September 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Relapsed or refractory paediatric B-cell ALL 1) 2nd or greater bone marrow (BM) relapse or 2) Relapse after remission for the first time in 12 months or 3) The interval between relapse after allogeneic hematopoietic stem cell transplantation and CAR-T cells transfusion≥100 days or 4) Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukaemia or 5) Patients with Philadelphia chromosome positive ALL were eligible if they were intolerant to or had failed two lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy was contraindicated or 6) Ineligible for allogeneic SCT because of: i. Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen iii. Lack of suitable donor iv. Prior SCT v. Declined allogeneic SCT as a therapeutic option after documented discussion, including expected outcomes, about the role of SCT with a BM transplantation physician not part of the study team
  2. For relapsed patients, CD19 tumour expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry
  3. Aged 2-70 years
  4. Eastern cooperative oncology group (ECOG) performance status of 0 to 2
  5. Life expectancy≥12 weeks
  6. Adequate organ function defined as:1) Creatinine clearance (as estimated by Cockcroft Gault) >60 mL/min. 2) Serum ALT/AST<2.5 ULN. 3) Total bilirubin<1.5 mg/dl, except in subjects with Gilbert's syndrome. 4) Cardiac ejection fraction≥45%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings. 5) No clinically significant pleural effusion. 6) Baseline oxygen saturation >92% on room air. 7) pulmonary function: ventilation function is normal or is restricted mildly.
  7. 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 6 months after cell transfusion therapy.
  8. The subject agree 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. Patients with Burkitt's lymphoma/leukaemia;
  3. Central nervous system leukemia involved CNS3;
  4. Concomitant malignancy other than non-melanoma skin cancer or adequately-treated cervical carcinoma in situ or prostate cancer (PSA score<1.0) or adequately-treated low grade bladder cancer or surgery-cured ductal carcinoma in situ or diagnosis of other malignancy exceeds 5 years without relapse or treatment during the 5 years;
  5. Concomitant genetic diseases except Down syndrome;
  6. Any result of the following virology tests is positive: HIV; HCV; HBsAg; or HBCAb positive with HBV DNA copies positive(≥ 5×10^2 copies/ml); RPR+TPPA postive;
  7. Live vaccine ≤4 weeks prior to apheresis;
  8. Presence of grade 2 to 4 graft-versus-host disease (GVHD) after allo-HSCT;
  9. The following medications were excluded: 1) Steroids: Therapeutic systemic doses of steroids must be stopped >72 hours prior to tisagenlecleucel infusion. However, the following physiological replacement doses of steroids are allowed: <12 mg/m^2/day hydrocortisone or equivalent; 2) Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed >6 weeks prior to tisagenlecleucel infusion; 3) GVHD therapies: Any systemic drug used for GVHD must be stopped >4 weeks prior to infusion to confirm that GVHD recurrence is not observed;
  10. Preventive treatments of CNS diseases must be stopped >3 days prior to infusion (e.g., intrathecal injection of methotrexate) 1) Radiotherapy of non-CNS nidus must be completed >2 weeks prior to infusion; 2) CNS stereotactic radiotherapy must be completed >8 weeks prior to infusion;
  11. ≥2 grade toxicities related to previous therapy are not relieved, with the exception of adverse events without security risk (e.g., alopecia);
  12. Known life-threatening allergy, hypersensitivity or intolerance to GC022 cells and adjuvant, including DMSO (see investigator's brochure);
  13. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogren syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease) receive immunosuppressive therapy in 4 weeks before inclusion. thyroid hormone replacement therapy is an exception;
  14. For patients that underwent major surgical operation before CAR-T treatment, or anticipated to undergo a major surgical operation during the study process, they need to be fully recovered and clinically stable before inclusion.
  15. Participate in other clinical trial and received study drugs <28 days prior to inclusion;
  16. Concomitant disease that may or severe medical condition that may affect patients' safety, including active viral or bacterial infection, uncontrollable systemic fungal infection, uncontrollable cardiac disease, hypertension, abuse of psychoactive drugs, et al.
  17. Any other condition that may increase subjects' risk or interfere with trial's results.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03825731
Other Study ID Numbers  ICMJE PGC0003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hebei Yanda Ludaopei Hospital
Study Sponsor  ICMJE Hebei Yanda Ludaopei Hospital
Collaborators  ICMJE Gracell Biotechnology Ltd.
Investigators  ICMJE Not Provided
PRS Account Hebei Yanda Ludaopei Hospital
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP