CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03233854|
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : May 20, 2022
|Condition or disease||Intervention/treatment||Phase|
|B Acute Lymphoblastic Leukemia CD19 Positive Minimal Residual Disease Philadelphia Chromosome Positive||Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Other: Questionnaire Administration Drug: NKTR-255||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 B cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen.
III. Assess the safety and feasibility of administering repeated doses of NKTR-255 intravenously after CD19/CD22-CAR T cell infusions in adults with ALL using a dose escalation design.
IV. Determine the recommended phase 2 dose (RP2D) of NKTR-255 when administered following CD19/CD22-CAR T cell infusion in adults with ALL
I. Evaluate the ability of CD19/CD22 CAR T cells to mediate clinical activity in adults with DLBCL and adults with ALL.
II. Characterize the pharmacokinetics (PK) of NKTR-255 when administered post CD19/CD22 CAR T cell infusion.
III. Explore the rate of relapse, progression free survival (PFS) and overall survival (OS) in subjects receiving CD19/CD22 CAR T cells, followed by up to 6 cycles of NKTR-255
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 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, NKTR-255)
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. On Day 14 after CAR-T, eligible patients will be given NKTR-255 IV over 30 minutes, and it will be repeated every 28 days for up to 6 cycles. 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 leukemia 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, CD22 and/or NKTR-255 [ Time Frame: Up to 15 years ]Will be evaluated.
- Immunogenicity of NKTR-255 [ Time Frame: Up to 15 years ]Will be evaluated when administered post CD19/CD22 CAR T cell infusion.
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: Maria Iglesiasfirstname.lastname@example.org|
|United States, California|
|Stanford University, School of Medicine||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Maria Iglesias 650-723-4247 email@example.com|
|Sub-Investigator: David B. Miklos, MD, PhD|
|Principal Investigator: Lori Muffly, MD, MS|
|Sub-Investigator: Laura Johnston, MD|
|Sub-Investigator: Everett Meyer, MD, PhD|
|Sub-Investigator: Andrew Rezvani, MD|
|Sub-Investigator: Wen Kai Weng, MD, PhD|
|Sub-Investigator: Matthew Frank, MD, PhD|
|Sub-Investigator: Wes (Janice) Brown, MD|
|Sub-Investigator: Sushma Bharadwaj, MD|
|Sub-Investigator: Sally Arai, MD|
|Sub-Investigator: Robert Lowsky, MD|
|Sub-Investigator: Robert Negrin, MD|
|Sub-Investigator: Judith Shizuru, MD, PhD|
|Sub-Investigator: Praveen Shiraz, MD|
|Sub-Investigator: Surbhi Sidana, MD|
|Sub-Investigator: Melody Smith, MD, MS|
|Principal Investigator:||Lori Muffly, MD, MS||Stanford University|