September 7, 2017
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September 11, 2017
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July 13, 2022
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December 5, 2017
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November 16, 2024 (Final data collection date for primary outcome measure)
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Dose-limiting toxicity [ Time Frame: Up to 28 days ] Will be graded by Common Terminology Criteria for Adverse Events version 4.0.
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Same as current
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- Complete remission [ Time Frame: Up to 15 years ]
Will be assessed based on the Lugano criteria.
- Progression-free survival (PFS) [ Time Frame: Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years ]
A Cox proportional hazards model will be used to evaluate PFS.
- Overall survival (OS) [ Time Frame: Duration from study enrollment to death due to any cause, assessed up to 15 years ]
A Cox proportional hazards model will be used to evaluate OS.
- Incidence of adverse events [ Time Frame: Up to 15 years ]
Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
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Not Provided
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Not Provided
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A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
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A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
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The purpose of this research is to find the best dose of genetically modified T-cells, to study the safety of this treatment, and to see how well it works in treating patients with B cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous treatment (refractory).
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OUTLINE:
This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy.
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide intravenously (IV). Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
Patients will be actively participating in the study for approximately 15 months. The total time includes the time for the T cells to be made, the T cell infusion, and for approximately 12 months after the T cell infusion is given. After completion of study treatment, patients are followed up for a minimum of 15 years.
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Interventional
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Phase 1 Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Recurrent B-Cell Non-Hodgkin Lymphoma
- Recurrent Chronic Lymphocytic Leukemia
- Recurrent Diffuse Large B-Cell Lymphoma
- Recurrent Follicular Lymphoma
- Recurrent Lymphoplasmacytic Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Refractory B-Cell Non-Hodgkin Lymphoma
- Refractory Diffuse Large B-Cell Lymphoma
- Refractory Follicular Lymphoma
- Refractory Lymphoplasmacytic Lymphoma
- Refractory Mantle Cell Lymphoma
- Refractory Transformed Non-Hodgkin Lymphoma
- Recurrent Transformed B-Cell Non-Hodgkin Lymphoma
- Recurrent Transformed Chronic Lymphocytic Leukemia
- Refractory Marginal Zone Lymphoma
- Refractory Transformed B-Cell Non-Hodgkin Lymphoma
- Refractory Transformed Chronic Lymphocytic Leukemia
- Recurrent Small Lymphocytic Lymphoma
- Refractory Chronic Lymphocytic Leukemia
- Refractory Small Lymphocytic Lymphoma
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- Biological: Chimeric Antigen Receptor T-Cell Therapy
Given CD20 CAR T cell IV
Other Names:
- CAR T-cell therapy
- CAR T Infusion
- CAR T Therapy
- Drug: Cyclophosphamide
Given IV
Other Names:
- (-)-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
- Other: Laboratory Biomarker Analysis
Correlative studies
- Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
- Leukocytopheresis
- Therapeutic Leukopheresis
- Drug: Fludarabine Phosphate
Given IV
Other Names:
- 2-F-ara-AMP
- Beneflur
- Fludara
- Fludarabine-5''-Monophosphate
- SH T 586
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Experimental: Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.
Interventions:
- Biological: Chimeric Antigen Receptor T-Cell Therapy
- Drug: Cyclophosphamide
- Other: Laboratory Biomarker Analysis
- Procedure: Leukapheresis
- Drug: Fludarabine Phosphate
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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.
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Recruiting
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35
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30
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November 16, 2037
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November 16, 2024 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
-
Patients must have B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Eligible lymphoma subtypes include (but not limited to): mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chronic lymphoid leukemia [CLL]), or diffuse large B cell lymphoma that has relapsed after a response to at least one prior therapy regimen or is refractory to prior therapy; patients with mantle cell lymphoma must have previously been treated with a Bruton tyrosine kinase (BTK) inhibitor and have either had disease progression, intolerance, or exposure to the drug for at least 3 months; patients with CLL/SLL are eligible if they had disease progression or intolerance to BTKis and/or a BCL-2 inhibitors; they are also required to have been treated with the other agent for at least 3 months (i.e. patients with progression/intolerance to BTKi need to be treated with a BCL-2 inhibitor for at least 3 months, and patients with progression/intolerance to BCL-2 inhibitor need at least 3 months of exposure to a BTKi); patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:
- Patients must be 18 years of age or older, of any gender, race or ethnicity
- Patients must be capable of understanding and providing a written informed consent
- Negative serum pregnancy test within 2 weeks before enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
- Fertile male and female patients must be willing to use an effective contraceptive method before, during, and for at least 4 months after the CAR T cell infusion
- Patients must have a Karnofsky performance status of >= 60%
- Confirmation of diagnosis by internal pathology review of initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)/University of Washington (UW)/Harborview Medical Center (HMC)
- Evidence of CD20 expression by immunohistochemistry or flow cytometry on the tumor specimen obtained with the biopsy performed with screening; if the CD20 expression on the screening tumor biopsy is unclear or could not be assessed due to technical reasons, CD20 expression on a concomitant tumor specimen (such as marrow biopsy or circulating tumor cells) may be used to satisfy this requirement
- Serum creatinine =< 2.5
- Total bilirubin =< 3.0 mg/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x the upper limit of normal
- Adequate pulmonary function, defined as =< grade 1 dyspnea and saturated oxygen (SaO2) >= 92% on room air; if pulmonary function test (PFT)s are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in 1 second (FEV1) >= 50% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of >= 40% of predicted will be eligible
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of >= 50% as assessed by echocardiogram or multigated acquisition (MUGA) scan, or LVEF of 45-49% and clearance by a cardiologist
- Measurable disease that can be accurately measured in at least one dimension as >= 2.0 cm with computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI) techniques; extranodal disease that is measurable by fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) imaging only will also be allowed; note that if an excisional biopsy was performed that removed the sole site of measurable disease, the patient will not be eligible for leukapheresis and generation of CAR T cell product
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with antibiotics, antiviral agents, or antifungal agents
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of active autoimmune disease requiring ongoing systemic immunosuppressive therapy
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Negative serum pregnancy test within 2 weeks before lymphodepletion chemotherapy for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: No treatment with any investigational agent on a different clinical trial between enrollment and lymphodepleting chemotherapy
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Serum creatinine =< 2.5
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Total bilirubin =< 3.0 mg/dL
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: AST and ALT =< 5 x the upper limit of normal
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate pulmonary function, defined as =< grade 1 dyspnea and SaO2 >= 92% on room air; if PFTs are performed based on the clinical judgment of the treating physician, patients with FEV1 >= 50% of predicted and DLCO (corrected) of >= 40% of predicted will be eligible
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of >= 50% as assessed by echocardiogram or MUGA scan, or LVEF of 45-49% and clearance by a cardiologist; if subject receives cardiotoxic chemotherapy after enrollment, repeat echocardiogram or MUGA is required to reestablish eligible LVEF
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have a Karnofsky performance status of >= 60%
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Measurable disease that can be accurately measured in at least one dimension as >= 2.0 cm with CT, ultrasound, or MRI techniques; extranodal disease that is measurable by FDG-PET imaging only will also be allowed; note that if an excisional biopsy was performed that removed the sole site of measurable disease, the patient is not be eligible for lymphodepletion and CAR T cell infusion; measurable disease can be based on the imaging study done during the screening unless the patient received treatment in the interim, in which case imaging should be repeated
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must require no corticosteroid therapy or dose of less than 15 mg per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable until the day before the start of lymphodepletion
- ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have no active acute or chronic GVHD
Exclusion Criteria:
- Active autoimmune disease requiring systemic immunosuppressive therapy
- Patients requiring corticosteroid therapy at a dose of 15 mg or more per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable
- Patients who are human immunodeficiency virus (HIV) seropositive
- Women who are pregnant or breastfeeding
- Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (> New York Heart Association [NYHA] class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia
- History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
- History or presence of clinically relevant non-lymphoma central nervous system pathology, including seizures that are uncontrolled on anticonvulsant therapy (>= 1 seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, or psychosis
- Treatment with any investigational agent on a different clinical trial within 4 weeks prior to enrollment, unless the patient is documented to be unresponsive to the therapy and at least 3 half-lives have elapsed prior to enrollment
- Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks before enrollment
- Previous treatment with CD19-targeted CAR T cells that has resulted in ongoing B cell aplasia at the time of enrollment; patients that demonstrate recovery of normal B cells (>= 20 B cells/ul) by flow cytometry at any point 28 days or later after CD19 CAR T cell infusion will be considered to have functional loss of CD19 CAR T cells and are potentially eligible
- Known active central nervous system metastases and/or lymphomatous meningitis; patients with isolated cerebrospinal fluid (CSF) involvement detectable by flow cytometry are eligible if clinically asymptomatic and if abnormal B cells are reported to be less than 3% by flow cytometry; subjects with previously treated central nervous system (CNS) disease may participate provided: 1) any CNS-directed treatment was completed at least 1 month prior to enrollment, 2) imaging studies and CSF evaluation show no evidence of disease progression, and 3) any neurologic symptoms have returned to baseline
- Presence of active acute or chronic graft versus host disease (GVHD)
- Uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with intravenous antibiotics, antiviral or antifungal agents
- Patients with concurrent known additional malignancy that is progressing and/or requires active treatment; exceptions include squamous or basal cell carcinoma of the skin and low grade prostate carcinoma (Gleason grade =< 6). Maintenance anti-hormone therapies for breast or prostate cancers are allowed and are not considered active treatment
- Patients with blood or platelet transfusion within 1 week prior to signing Consent A, or with platelets < 50,000/mm^3, neutrophils < 750/mm^3, or hemoglobin < 8.5 g/dL, unless the cytopenias are considered by the treating physician to be largely due to marrow involvement by lymphoma
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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United States
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NCT03277729
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9738 NCI-2017-01595 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 9738 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) RG9217017 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Fred Hutchinson Cancer Center
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Same as current
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Fred Hutchinson Cancer Center
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Same as current
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Mustang Bio
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Principal Investigator: |
Mazyar Shadman |
Fred Hutch/University of Washington Cancer Consortium |
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Fred Hutchinson Cancer Center
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July 2022
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