Condition or disease | Intervention/treatment | Phase |
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CD19 Positive CD20 Positive Recurrent Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Mantle Cell Lymphoma Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma Refractory Small Lymphocytic Lymphoma | Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Phosphate Biological: Tocilizumab | Phase 1 |
PRIMARY OBJECTIVES:
I. To evaluate the safety of the autologous anti-CD19/anti-CD20 CAR-expressing naive/memory T cells (CART19/20), including determination of the maximum tolerated dose and assessment for replication competent lentivirus (RCL).
SECONDARY OBJECTIVES:
I. Clinical response. Ia. Overall response rate. Ib. Duration of remission. Ic. Progression-free survival. Id. Overall survival. II. CD19/CD20 bispecific CAR transgenic T-cell persistence. IIa. T-cell monitoring and analyses. IIb. Evidence of B-cell aplasia.
EXPLORATORY OBJECTIVES:
I. To determine the serum levels of cytokines associated with cytokine release syndrome (CRS) in subjects exhibiting > grade-2 CRS following CART19/20 cell treatment.
OUTLINE: This is a dose-escalation study of CD19/CD20 CAR-T cells.
CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion.
T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator.
After completion of study treatment, patients are followed up daily for 14 days, on days 30, 45, 60, 70, 90, and 120, every 3 months for 2 years, every 6 months for 3 years, and then annually for a minimum of 15 years.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 24 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Study of CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for the Treatment of Relapsed or Refractory B-Cell Lymphomas and Chronic Lymphocytic Leukemia (CD20 - Cluster of Differentiation Antigen 20) |
Actual Study Start Date : | October 4, 2019 |
Estimated Primary Completion Date : | August 1, 2022 |
Estimated Study Completion Date : | August 1, 2023 |
Arm | Intervention/treatment |
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Experimental: Treatment (fludarabine, cyclophosphamide, CD19/CD20 T-cells)
CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion. T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator. |
Biological: Chimeric Antigen Receptor T-Cell Therapy
Given Autologous anti-CD19/anti-CD20 CAR-expressing naive/memory T cells IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Biological: Tocilizumab Given IV
Other Names:
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Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL) that is refractory to standard-of-care options
Exclusion Criteria:
History of other malignancy in the past 3 years with the following exceptions:
Contact: Bruck Habtemariam | 310 794-0242 | BHabtemariam@mednet.ucla.edu |
United States, California | |
UCLA / Jonsson Comprehensive Cancer Center | Recruiting |
Los Angeles, California, United States, 90095 | |
Contact: Bruck Habtemariam 310-794-0242 BHabtemariam@mednet.ucla.edu | |
Principal Investigator: Sarah Larson, M.D. |
Principal Investigator: | Sarah Larson, MD | UCLA / Jonsson Comprehensive Cancer Center |
Tracking Information | |||||||
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First Submitted Date ICMJE | June 20, 2019 | ||||||
First Posted Date ICMJE | July 5, 2019 | ||||||
Last Update Posted Date | November 19, 2020 | ||||||
Actual Study Start Date ICMJE | October 4, 2019 | ||||||
Estimated Primary Completion Date | August 1, 2022 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Analysis of proteins/cytokines (c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)) concentration in peripheral blood following CART19/20 infusion. [ Time Frame: Up to 30 days post-infusion ] The cytokine levels in patients who receive CAR therapies will be monitored to help clarify the complex relationship between CRS severity, toxicity, T-cell survival, and disease eradication. Cytokine levels will be quantified in patients exhibiting any > grade-2 CRS. Cytokine levels in patients who do not exhibit CRS, or exhibit =< grade-2 CRS, will be quantified at the discretion of the investigator. The concentration in blood of each protein will be measured (CRP: mg/dL; IL-6, TNF-α, IFN-γ: pg/mL).
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Original Other Pre-specified Outcome Measures | Same as current | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia | ||||||
Official Title ICMJE | Study of CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for the Treatment of Relapsed or Refractory B-Cell Lymphomas and Chronic Lymphocytic Leukemia (CD20 - Cluster of Differentiation Antigen 20) | ||||||
Brief Summary | This phase I trial studies the side effects and best dose of CD19/CD20 chimeric antigen receptor (CAR) T-cells when given together with chemotherapy, and to see how effective they are in treating patients with non-Hodgkin's B-cell lymphoma or chronic lymphocytic leukemia that has come back (recurrent) or has not responded to treatment (refractory). In CAR-T cell therapy, a patient's white blood cells (T cells) are changed in the laboratory to produce an engineered receptor that allows the T cell to recognize and respond to CD19 and CD20 proteins. CD19 and CD20 are commonly found on non-Hodgkin?s B-cell lymphoma and chronic lymphocytic leukemia cells. Chemotherapy drugs such as fludarabine phosphate and cyclophosphamide can control cancer cells by killing them, by preventing their growth, or by stopping them from spreading. Combining CD19/CD20 CAR-T cells and chemotherapy may help treat patients with recurrent or refractory B-cell lymphoma or chronic lymphocytic leukemia. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: I. To evaluate the safety of the autologous anti-CD19/anti-CD20 CAR-expressing naive/memory T cells (CART19/20), including determination of the maximum tolerated dose and assessment for replication competent lentivirus (RCL). SECONDARY OBJECTIVES: I. Clinical response. Ia. Overall response rate. Ib. Duration of remission. Ic. Progression-free survival. Id. Overall survival. II. CD19/CD20 bispecific CAR transgenic T-cell persistence. IIa. T-cell monitoring and analyses. IIb. Evidence of B-cell aplasia. EXPLORATORY OBJECTIVES: I. To determine the serum levels of cytokines associated with cytokine release syndrome (CRS) in subjects exhibiting > grade-2 CRS following CART19/20 cell treatment. OUTLINE: This is a dose-escalation study of CD19/CD20 CAR-T cells. CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion. T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator. After completion of study treatment, patients are followed up daily for 14 days, on days 30, 45, 60, 70, 90, and 120, every 3 months for 2 years, every 6 months for 3 years, and then annually for a minimum of 15 years. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (fludarabine, cyclophosphamide, CD19/CD20 T-cells)
CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion. T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator. Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
24 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | August 1, 2023 | ||||||
Estimated Primary Completion Date | August 1, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04007029 | ||||||
Other Study ID Numbers ICMJE | 18-001989 NCI-2019-03190 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 18-001989 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Jonsson Comprehensive Cancer Center | ||||||
Study Sponsor ICMJE | Jonsson Comprehensive Cancer Center | ||||||
Collaborators ICMJE | Parker Institute for Cancer Immunotherapy | ||||||
Investigators ICMJE |
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PRS Account | Jonsson Comprehensive Cancer Center | ||||||
Verification Date | November 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |