Back to resultsCD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
Primary Purpose
B Cell Lymphoma, B Cell Leukemia
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Autologous 3rd generation CD19-targeting CAR T cells
Sponsored by
About this trial
This is an interventional treatment trial for B Cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
- Measurable disease.
- Performance status ECOG 0-2.
- >18 years old.
- Fertile females/males must consent to use contraceptives during participation of the trial.
- Signed informed consent.
Exclusion Criteria:
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with primary CNS lymphoma.
- Known human immunodeficiency virus (HIV) infection.
- Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
- Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
- Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half lives of that drug, which is longest.
- Patients that do not consent to that tissue and blood samples are stored in a biobank.
- Pregnancy
Sites / Locations
- Uppsala University Hospital, Dept of Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CAR T cells
Arm Description
Autologous 3rd generation CD19-targeting CAR T cells
Outcomes
Primary Outcome Measures
CAR T cell persistence
Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood.
Secondary Outcome Measures
Tumor load
Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
Full Information
NCT ID
NCT02132624
First Posted
May 5, 2014
Last Updated
October 27, 2017
Sponsor
Uppsala University
Collaborators
Uppsala University Hospital, Karolinska University Hospital, AFA Insurance, Swedish Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT02132624
Brief Title
CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
Official Title
CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
May 31, 2017 (Actual)
Study Completion Date
May 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
Collaborators
Uppsala University Hospital, Karolinska University Hospital, AFA Insurance, Swedish Cancer Society
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell lymphoma or leukemia. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B Cell Lymphoma, B Cell 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
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CAR T cells
Arm Type
Experimental
Arm Description
Autologous 3rd generation CD19-targeting CAR T cells
Intervention Type
Biological
Intervention Name(s)
Autologous 3rd generation CD19-targeting CAR T cells
Intervention Description
Autologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB.
Primary Outcome Measure Information:
Title
CAR T cell persistence
Description
Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood.
Time Frame
At week 1 and 5, there after every 3 months post treatment up to 24 months
Secondary Outcome Measure Information:
Title
Tumor load
Description
Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
Time Frame
Every 3 months post treatment up to 24 months
Other Pre-specified Outcome Measures:
Title
B cell number and immunoglobulins
Description
Number of blood B cells and immunoglobulins will be evaluated by routine diagnostics
Time Frame
Weekly for 5 weeks, then every 3 months post treatment up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
Measurable disease.
Performance status ECOG 0-2.
>18 years old.
Fertile females/males must consent to use contraceptives during participation of the trial.
Signed informed consent.
Exclusion Criteria:
Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
Patients with primary CNS lymphoma.
Known human immunodeficiency virus (HIV) infection.
Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half lives of that drug, which is longest.
Patients that do not consent to that tissue and blood samples are stored in a biobank.
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angelica Loskog, PhD
Organizational Affiliation
Uppsala University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Gunilla Enblad, MD, PhD
Organizational Affiliation
Uppsala University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hans Hagberg, MD, PhD
Organizational Affiliation
Uppsala University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uppsala University Hospital, Dept of Oncology
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
34515338
Citation
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Results Reference
derived
PubMed Identifier
30097433
Citation
Enblad G, Karlsson H, Gammelgard G, Wenthe J, Lovgren T, Amini RM, Wikstrom KI, Essand M, Savoldo B, Hallbook H, Hoglund M, Dotti G, Brenner MK, Hagberg H, Loskog A. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin Cancer Res. 2018 Dec 15;24(24):6185-6194. doi: 10.1158/1078-0432.CCR-18-0426. Epub 2018 Aug 10.
Results Reference
derived
Learn more about this trial
CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
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