CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT03233854|
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : February 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|B Acute Lymphoblastic Leukemia CD19 Positive Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly Minimal Residual Disease Philadelphia Chromosome Positive Recurrent Diffuse Large B-Cell Lymphoma Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma T-Cell/Histiocyte-Rich Large B-Cell Lymphoma||Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Other: Questionnaire Administration||Phase 1|
I. Determine the feasibility of producing CD19/CD22-CAR T cells meeting the established release criteria.
II. Assess the safety of administering escalating doses of autologous CD19/CD22-CAR T cells that meet established release specifications in adults with hematologic malignancies following a cyclophosphamide/fludarabine phosphate (fludarabine) conditioning regimen.
I. Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in adults with B cell malignancies.
I. Evaluate the frequency of CD22+ expression on lymphoma cells, and determine site density when possible.
II. Analyze alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells.
III. Evaluate whether subjects receiving CD19/CD22-CAR T cells relapse with loss or diminished expression of CD19 and/or CD22, when feasible.
IV. Measure persistence of CD19/CD22-CAR T cells in the blood, bone marrow and cerebrospinal fluid (CSF), and explore correlations between anti CD19/CD22-CAR T cell properties and CAR T cell efficacy and persistence.
V. Establish the utility of chromatin structure and epigenomic technology to characterize CAR T cell therapies.
OUTLINE: This is a dose-escalation study of CD19/CD22-CAR T cells.
Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.
After completion of study treatment, patients are followed up daily until day 14, twice per week until day 28, at 2 months, at 3 months, every 3 months until month 12, every 6-12 months up to year 5, and then annually for years 6-15.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Malignancies|
|Actual Study Start Date :||September 1, 2017|
|Estimated Primary Completion Date :||September 1, 2025|
|Estimated Study Completion Date :||September 1, 2035|
Experimental: Treatment (CD19/CD22 CAR T cells, chemotherapy)
Patients receive cyclophosphamide IV over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive CD19/CD22 CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22 CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22 CAR T cells.
Biological: Chimeric Antigen Receptor T-Cell Therapy
Given CD19/CD22 CAR T cells IV
Other Name: CAR T-cell therapy
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
- Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 28 days ]Safety data will be analyzed per standard methods and interpreted descriptively for each dose cohort. Safety data will be summarized for each dose cohort separately and for all dose cohorts combined. Adverse events will be assessed using the CTCAE version 4.03 for type and severity of event. Serious Adverse Events will be summarized for each dose cohort and for all dose cohorts combined. Reasons for discontinuation of study therapy will be tabulated.
- Maximum tolerated dose of CD19/CD22 chimeric antigen receptor (CAR) T cells defined as the dose level immediately below the level at which the enrollment is stopped due to a dose limiting toxicity [ Time Frame: Up to 28 days ]Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis [ Time Frame: Up to 15 years ]In addition to aiming to evaluate up to 6 subjects at a given dose level with respect to toxicity, the number of subjects which can successfully manufacture the targeted dose number will be determined.
- Overall survival [ Time Frame: From the start of the preparative regimen until death, assessed for up to 15 years ]Will be assessed by dose cohort.
- Progression free survival [ Time Frame: From the start of the preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed for up to 15 years ]Will be assessed by dose cohort.
- The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 15 years ]Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia.
- Alterations in early B cell development induced by immune pressure exerted via CD19/CD22 chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 15 years ]Will be evaluated.
- CD19/CD22 chimeric antigen receptor (CAR) T cell properties [ Time Frame: Up to 15 years ]Will explore correlations with CAR T cell efficacy and persistence.
- Establish the utility of chromatin structure and epigenomic technology to characterize chimeric antigen receptor (CAR) T cell therapies [ Time Frame: Up to 15 years ]Investigators will attempt to establish parameters for how best to utilize the technology in CAR research to: establish basis for blood therapeutic monitoring; derive blood biomarkers for prediction of the safety and efficacy of CAR cell therapy; and develop metrics for CAR T product release criteria that can be used during the manufacturing of the product.
- Frequency of CD22+ expression on lymphoma cells [ Time Frame: Up to 15 years ]Will correlate with clinical response to CAR T cells.
- Persistence of CD19/CD22 chimeric antigen receptor (CAR) T cells blood, bone marrow, and cerebral spinal fluid [ Time Frame: Up to 15 years ]Will be assessed by flow cytometry. Will be analyzed and reported as time from T cell infusion.
- Relapse with loss or diminished expression of CD19 and/or CD22 [ Time Frame: Up to 15 years ]Will be evaluated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03233854
|Contact: Juliana Craigemail@example.com|
|United States, California|
|Stanford University, School of Medicine||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Juliana Craig 650-736-0912 firstname.lastname@example.org|
|Principal Investigator: David B. Miklos|
|Principal Investigator:||David Miklos||Stanford University|