A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
Primary Purpose
B-cell Acute Lymphoblastic Leukemia
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
GC019F
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Aged 18-70 years;
- Eastern cooperative oncology group (ECOG) performance status of 0 to 2;
- Life expectancy≥12 weeks;
- CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry;
- 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.
- Did not receive hematopoietic stem cell transplantation≤6 months prior to enrollment;
- 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;
- 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;
- Venous access can be established, peripheral blood mononuclear cells (PBMC) can be collected in researcher's judgement;
- The subject agrees to and sign informed consent form;
- 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:
- Isolated extramedullary leukemia or isolated extramedullary disease relapse;
- Central nervous system leukemia involved CNS3;
- 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;
- Any result of the following infectious disease tests is positive: HIV; HCV; HBsAg; or HBcAb positive with HBV DNA copies positive; TPPA;
- Live vaccine ≤4 weeks prior to enrollment;
- For Ph+ ALL, TKI therapy ≤1 week prior to enrollment;
- History of anti-CD19 therapy or CAR-T or other gene-editing T cell therapy;
- 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;
- 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;
- CNS stereotactic radiotherapy ≤4 weeks prior to enrollment;
- Toxicities related to previous therapy did not relieved to ≤1 grade, except hematological toxicity and alopecia;
- Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or presence of other intolerant conditions, or severe allergic constitution;
- 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);
- 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;
- Took drug from other research≤28 days prior to enrollment;
- 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;
- 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;
- Any other condition that researcher think it is inappropriate for the subject to anticipate the trial.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CAR-T treatment group
Arm Description
The patients will receive one dose of GC019F.
Outcomes
Primary Outcome Measures
Incidence and severity of adverse events(AE)
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
CAR copies and concentration of GC007F in peripheral blood, bone marrow and CSF
GC007F CAR copies and cells in peripheral blood, bone marrow and CSF will be measured by qPCR and FCM in 2 years
Overall response rate (ORR) and minimal residual disease negative (MRD-) rate of patients who received GC007F infusion
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).
Duration of response (DOR), progression-free survival (PFS), overall survival (OS) of patients who received GC007F infusion
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.
Concentration of anti-GC007F antibody after infusion
After GC007F infusion, GC007F antibody in peripheral blood will be measured in 2 years
Full Information
NCT ID
NCT04595162
First Posted
October 14, 2020
Last Updated
October 14, 2020
Sponsor
Peking University Third Hospital
Collaborators
Gracell Biotechnology Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04595162
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 15, 2021 (Anticipated)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
December 15, 2035 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University Third Hospital
Collaborators
Gracell Biotechnology Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Acute Lymphoblastic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CAR-T treatment group
Arm Type
Experimental
Arm Description
The patients will receive one dose of GC019F.
Intervention Type
Biological
Intervention Name(s)
GC019F
Intervention Description
GC019F is the CAR-T cell immunotherapy targeted CD19. The subjects will receive one single infusion of GC019F.
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events(AE)
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 )
Time Frame
15 years
Secondary Outcome Measure Information:
Title
CAR copies and concentration of GC007F in peripheral blood, bone marrow and CSF
Description
GC007F CAR copies and cells in peripheral blood, bone marrow and CSF will be measured by qPCR and FCM in 2 years
Time Frame
2 years
Title
Overall response rate (ORR) and minimal residual disease negative (MRD-) rate of patients who received GC007F infusion
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).
Time Frame
2 years
Title
Duration of response (DOR), progression-free survival (PFS), overall survival (OS) of patients who received GC007F infusion
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.
Time Frame
15 years
Title
Concentration of anti-GC007F antibody after infusion
Description
After GC007F infusion, GC007F antibody in peripheral blood will be measured in 2 years
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18-70 years;
Eastern cooperative oncology group (ECOG) performance status of 0 to 2;
Life expectancy≥12 weeks;
CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry;
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.
Did not receive hematopoietic stem cell transplantation≤6 months prior to enrollment;
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;
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;
Venous access can be established, peripheral blood mononuclear cells (PBMC) can be collected in researcher's judgement;
The subject agrees to and sign informed consent form;
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:
Isolated extramedullary leukemia or isolated extramedullary disease relapse;
Central nervous system leukemia involved CNS3;
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;
Any result of the following infectious disease tests is positive: HIV; HCV; HBsAg; or HBcAb positive with HBV DNA copies positive; TPPA;
Live vaccine ≤4 weeks prior to enrollment;
For Ph+ ALL, TKI therapy ≤1 week prior to enrollment;
History of anti-CD19 therapy or CAR-T or other gene-editing T cell therapy;
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;
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;
CNS stereotactic radiotherapy ≤4 weeks prior to enrollment;
Toxicities related to previous therapy did not relieved to ≤1 grade, except hematological toxicity and alopecia;
Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or presence of other intolerant conditions, or severe allergic constitution;
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);
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;
Took drug from other research≤28 days prior to enrollment;
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;
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;
Any other condition that researcher think it is inappropriate for the subject to anticipate the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongmei Jing, Doctor
Phone
15611908428
Email
hongmei_jing@163.com
12. IPD Sharing Statement
Learn more about this trial
A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
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