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

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.

Study Overview

• Status: Unknown
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: GC022

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Recruiting
      • Hebei yanda Ludaopei Hospital
      • Contact: Peihua Lu, PhD&MD; Phone Number: +86-0316-3306393; Email: Peihua_lu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GC022; The patients will receive GC022 CAR-T treatment. GC022 dosage ranges from 3×10^5 to 1×10^7 CAR+T/Kg.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Dose Limiting Toxicity	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	12 weeks
Incidence of adverse events	After GC022 infusion, adverse events will be graded as CTCAE 4.0	12 weeks
GC022 persistence	After GC022 infusion, GC022 CAR copies in peripheral blood. bone marrow and CSF will be measured by qPCR in 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percents of Patients with best response as complete remission and MRD negative complete remission	Response rates will be estimated as the percents of patients whose best response is complete remission and MRD negative complete remission	12 weeks

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital
• Collaborators: Gracell Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Anticipated): September 16, 2019
• Study Completion (Anticipated): September 16, 2019

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: PGC0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No