Back to resultsCD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
Primary Purpose
Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Blasts 5 Percent or More of Bone Marrow Nucleated Cells
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine Phosphate
Laboratory Biomarker Analysis
Tisagenlecleucel
Sponsored by
About this trial
This is an interventional treatment trial for Acute Biphenotypic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
- Confirmed history of CD19 positivity by flow cytometry for malignant cells
- Lansky/Karnofsky performance scale > 60%
- Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
- Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676
Exclusion Criteria:
- Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
- Patients with known allergy to bovine or murine products
- Positive serology for human immunodeficiency virus (HIV)
- Active hepatitis B or active hepatitis C
- Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
- Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; hematopoietic stem cell transplant (HSCT) > 3 months from CAR T cell infusion eligible
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I (CD19 positive chimeric antigen receptor T-cells)
Arm Description
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate IV over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician. Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
Outcomes
Primary Outcome Measures
Maximum tolerated dose of genetically modified, CD19-specified T cells
Will be defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Demographic and clinical characteristics will be summarized using descriptive statistics by dose level. The number of patients with dose limiting toxicities will be reported at each dose level.
Secondary Outcome Measures
The proportion of patients for which a T cell product could not be prepared
Computed with a corresponding 95% confidence interval.
Proportion of patients experiencing response (complete response and partial response)
Estimated with a corresponding 95% confidence interval.
Full Information
NCT ID
NCT02529813
First Posted
August 18, 2015
Last Updated
June 29, 2022
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Ziopharm Oncology
1. Study Identification
Unique Protocol Identification Number
NCT02529813
Brief Title
CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
Official Title
CD19+ Chimeric Antigen Receptor T Cells for Patients With Advanced Lymphoid Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
December 16, 2015 (Actual)
Primary Completion Date
November 8, 2021 (Actual)
Study Completion Date
November 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Ziopharm Oncology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells in treating patients with lymphoid malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. Sometimes researchers change the deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. Injecting modified T-cells made from the patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and maximum tolerated dose of genetically modified, CD19-specific T cells administered into patients with CD19+ advanced lymphoid malignancies.
SECONDARY OBJECTIVES:
I. To screen for the development of host immune responses against the CD19-specific chimeric antigen receptor (CAR).
II. To describe the homing ability of the infused T cells. III. To assess disease response. IV. To determine persistence of CAR+ T cells.
OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
After completion of study treatment, patients are followed up for at least 15 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Blasts 5 Percent or More of Bone Marrow Nucleated Cells, CD19 Positive, Minimal Residual Disease, Non-Hodgkin Lymphoma, Small Lymphocytic Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic 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
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (CD19 positive chimeric antigen receptor T-cells)
Arm Type
Experimental
Arm Description
LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate IV over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.
Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Tisagenlecleucel
Other Intervention Name(s)
CART-19, CART19, CTL019, CTL019 T-cells, Kymriah, Tisagenlecleucel-T
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerated dose of genetically modified, CD19-specified T cells
Description
Will be defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Demographic and clinical characteristics will be summarized using descriptive statistics by dose level. The number of patients with dose limiting toxicities will be reported at each dose level.
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
The proportion of patients for which a T cell product could not be prepared
Description
Computed with a corresponding 95% confidence interval.
Time Frame
Up to 1 year
Title
Proportion of patients experiencing response (complete response and partial response)
Description
Estimated with a corresponding 95% confidence interval.
Time Frame
Up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
Confirmed history of CD19 positivity by flow cytometry for malignant cells
Lansky/Karnofsky performance scale > 60%
Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676
Exclusion Criteria:
Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
Patients with known allergy to bovine or murine products
Positive serology for human immunodeficiency virus (HIV)
Active hepatitis B or active hepatitis C
Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; hematopoietic stem cell transplant (HSCT) > 3 months from CAR T cell infusion eligible
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Partow Kebriaei
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website
Learn more about this trial
CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
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