A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy
Primary Purpose
Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Specificity CD38 CAR-T Cells
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI
Eligibility Criteria
Inclusion Criteria:
- Male or female participant
- 12 Years to 70 Years (Child, Adult, Senior)
- Patient with relapsed CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy
- Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Adequate organ function
Exclusion Criteria:
- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
- Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
- Richter's syndrome
- Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
- Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
- Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- Patient has an investigational medicinal product within the last 30 days prior to screening
- Previous treatment with investigational gene or cell therapy medicine products
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Pregnant or nursing women
Sites / Locations
- Biotherapeutic Department and Hematology Department of Chinese PLARecruiting
Outcomes
Primary Outcome Measures
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
MTD of specificity CD38 CAR-T cells
The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells.
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
Secondary Outcome Measures
Six-month Objective response rate of complete remission and partial remission
Six-month Overall survival
Six-month Progression free survival
Full Information
NCT ID
NCT03754764
First Posted
November 24, 2018
Last Updated
December 5, 2018
Sponsor
Chinese PLA General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03754764
Brief Title
A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy
Official Title
Phase I/II Study to Evaluate Treatment of Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy With CAR-T Cells Targeting CD38
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 23, 2018 (Actual)
Primary Completion Date
November 23, 2022 (Anticipated)
Study Completion Date
November 23, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital
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
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD38. This is a phase 1/2 study designed to determine the safety of the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy.
Detailed Description
PRIMARY OBJECTIVES:
To evaluate the feasibility and safety of specificity CD38 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.
To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.
Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of CD38 CAR-T cells over time.
SECONDARY OBJECTIVES:
For patients with detectable disease, measure anti-tumor response due to specificity CD38 CAR-T cell infusions.
The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
Specificity CD38 CAR-T Cells
Intervention Description
1) Biological: Specificity CD38 CAR-T Cells 2) Day 0: 1-5x10e6/kg total dose .3) Other: Laboratory Biomarker Analysis
Primary Outcome Measure Information:
Title
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Time Frame
24 weeks
Title
MTD of specificity CD38 CAR-T cells
Description
The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells.
Time Frame
4 weeks
Title
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Six-month Objective response rate of complete remission and partial remission
Time Frame
24 weeks
Title
Six-month Overall survival
Time Frame
24 weeks
Title
Six-month Progression free survival
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participant
12 Years to 70 Years (Child, Adult, Senior)
Patient with relapsed CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy
Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Adequate organ function
Exclusion Criteria:
Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
Richter's syndrome
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
Patient has an investigational medicinal product within the last 30 days prior to screening
Previous treatment with investigational gene or cell therapy medicine products
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
Pregnant or nursing women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hejin Jia
Phone
86-10-55499341
Email
PLAGH@QQ.COM
First Name & Middle Initial & Last Name or Official Title & Degree
Zhitao Gao, Dr
Phone
86-010-66937917
Email
zhitaogao@qq.com
Facility Information:
Facility Name
Biotherapeutic Department and Hematology Department of Chinese PLA
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100083
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weidong Han, Dr
Phone
86-10-13651392893
Email
hanwdrsw@sina.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Feasibility and Safety Study of CD38 CAR-T Cell Immunotherapy for Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy
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