Back to resultsCD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.
Primary Purpose
B-cell Acute Lymphocytic Leukemia
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
CD19 CAR-T
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Acute Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- 1. 2 years to 70 years, expected survival > 3 months;
- 2. CD19 positive B-cell acute lymphoblastic leukemia;
- 3. ECOG < 2；
- 4. The tumor load in the bone marrow is less than 60%;
- 5. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; Peripheral Blood: WBC ≥ 2.0×109/L, Hb ≥80 g/L, PLT ≥ 30×109/L）;
- 6. No leukemia cells in the central nervous system;
- 7. No serious allergic constitution;
- 8. No other serous diseases that conflicts with the clinical program;
- 9. No other cancer history;
- 10. No serious mental disorder;
- 11. female participants of reproductive potential must have a negative serum pregnancy test;
- 12. Informed consent is signed by a subject or his lineal relation.
Exclusion Criteria:
- 1. Pregnant or lactating women;
- 2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
- 3. Active hepatitis B or hepatitis C infection;
- 4. Recent or current use of glucocorticoid or other immunosuppressor;
- 5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
- 6. Participate in other clinical research in the past three months; previously treatment with any gene therapy products;
Sites / Locations
- The First Affiliated Hospital of Henan University of Science and Technology
- Henan Cancer HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CD19 CAR-T
Arm Description
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Outcomes
Primary Outcome Measures
safety as assessed by the occurence of study related adverse events
number of participants with adverse events
anti-tumor responses of CD19 CAR-T cells
Secondary Outcome Measures
Persistence of the CD19 CAR+ T cells
determine duration of in vivo survival of CD19 CAR-T cells
Number of participants who have T cells ablated with cetuximab
The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.
Full Information
NCT ID
NCT03263208
First Posted
August 24, 2017
Last Updated
October 19, 2017
Sponsor
Henan Cancer Hospital
Collaborators
The Pregene (ShenZhen) Biotechnology Company, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03263208
Brief Title
CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.
Official Title
A Study of CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-cell Acute Lymphoblastic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
August 16, 2017 (Actual)
Primary Completion Date
January 2019 (Anticipated)
Study Completion Date
July 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Henan Cancer Hospital
Collaborators
The Pregene (ShenZhen) Biotechnology Company, Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to infusion CD19 CAR-T cells to the patients with relapsed and refractory CD19+ B cell leukemia, to assess the safety and feasibility of this strategy. The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia.
Detailed Description
Upon meeting the eligibility requirements and enrolling on study, Subjects will be collected large numbers of peripheral blood mononuclear cells (PBMC) for the generation of the CD19 CAR-T cells. The T cells are isolated from the PBMC, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in vitro and then administered to subjects.
Subjects will have blood tests to assess safety and efficacy, and persistence of the CD19 CAR-T cells on week 4 after their last infusion. Following the 6 months of intensive follow-up, subjects will be evaluated every 10 weeks for 1 year with a physical examination, blood tests, bone marrow aspirate, MRD and persistence of CD19 CAR-T.
Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Acute Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CD19 CAR-T
Arm Type
Experimental
Arm Description
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
patients will receive a standard pre-conditioning regime with cyclophosphamide 0.6-0.8g/m2/day IV for 2 days(Day-5 to day-4).
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 25-30mg/m2/day IV for 3 days(Day-5 to day-3).
Intervention Type
Biological
Intervention Name(s)
CD19 CAR-T
Intervention Description
CD19 CAR-T cells will be administered after completion of the chemotherapy.
Primary Outcome Measure Information:
Title
safety as assessed by the occurence of study related adverse events
Description
number of participants with adverse events
Time Frame
30 days
Title
anti-tumor responses of CD19 CAR-T cells
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Persistence of the CD19 CAR+ T cells
Description
determine duration of in vivo survival of CD19 CAR-T cells
Time Frame
1 year
Title
Number of participants who have T cells ablated with cetuximab
Description
The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. 2 years to 70 years, expected survival > 3 months;
2. CD19 positive B-cell acute lymphoblastic leukemia;
3. ECOG < 2；
4. The tumor load in the bone marrow is less than 60%;
5. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; Peripheral Blood: WBC ≥ 2.0×109/L, Hb ≥80 g/L, PLT ≥ 30×109/L）;
6. No leukemia cells in the central nervous system;
7. No serious allergic constitution;
8. No other serous diseases that conflicts with the clinical program;
9. No other cancer history;
10. No serious mental disorder;
11. female participants of reproductive potential must have a negative serum pregnancy test;
12. Informed consent is signed by a subject or his lineal relation.
Exclusion Criteria:
1. Pregnant or lactating women;
2. Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
3. Active hepatitis B or hepatitis C infection;
4. Recent or current use of glucocorticoid or other immunosuppressor;
5. With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
6. Participate in other clinical research in the past three months; previously treatment with any gene therapy products;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongping Song
Phone
+86 13521186987
Email
ph200811@163.com
Facility Information:
Facility Name
The First Affiliated Hospital of Henan University of Science and Technology
City
Luoyang
State/Province
Henan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haiping Yang
Phone
+86 13938820189
Email
13938820189@163.com
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongping Song
Phone
+86 13521186987
Email
ph200811@163.com
12. IPD Sharing Statement
Learn more about this trial
CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.
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