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Trial record 10 of 23 for:    CD20 Fred Hutchinson | United States

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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ClinicalTrials.gov Identifier: NCT03277729
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : April 13, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
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 or did not respond to previous treatment.

Condition or disease Intervention/treatment Phase
CD20 Positive 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 Indolent Non-Hodgkin Lymphoma Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Other: Laboratory Biomarker Analysis Procedure: Leukapheresis Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of adoptive cellular immunotherapy using ex vivo transduced and expanded autologous T cells expressing a third (3rd)-generation fully human CD20-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma (B-NHL).

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity associated with CD20 CAR T cell infusions.

II. To evaluate preliminary antitumor activity of adoptively transferred T cells in patients with measurable tumor burden prior to treatment as measured by overall response rate (ORR) and complete remission (CR) rate.

III. To evaluate progression-free survival (PFS) and overall survival (OS) among patients treated with adoptively transferred CD20-specific T cells.

OUTLINE: This is a phase I/II dose-escalation study of CD20-specific CAR T cell therapy.

Patients undergo leukapheresis and may receive low-intensity chemotherapy including lenalidomide or ibrutinib 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.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 5, 2017
Estimated Primary Completion Date : November 16, 2022
Estimated Study Completion Date : November 16, 2037


Arm Intervention/treatment
Experimental: Treatment (CD20-specific CAR T cell, chemotherapy)
Patients undergo leukapheresis. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion.
Biological: Chimeric Antigen Receptor T-Cell Therapy
Given CD20 CAR T cell IV
Other Name: CAR T-cell 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

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
  • Leukocytopheresis
  • Therapeutic Leukopheresis




Primary Outcome Measures :
  1. Dose-limiting toxicity [ Time Frame: Up to 28 days ]
    Will be graded by Common Terminology Criteria for Adverse Events version 4.0.


Secondary Outcome Measures :
  1. Complete remission [ Time Frame: Up to 15 years ]
    Will be assessed based on the Lugano criteria.

  2. Progression-free survival [ Time Frame: Duration from study registration to progression or death due to any cause (whichever comes first), assessed up to 15 years ]
  3. Overall survival [ Time Frame: Duration from study registration to death due to any cause, assessed up to 15 years ]
  4. 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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have B-cell non-Hodgkin lymphoma, including mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chromic 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 de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:

    • Biopsy-proven refractory disease after a frontline regimen containing both an anthracycline and rituximab or other anti-CD20 antibody (i.e. "primary refractory"), where any disease recurring within 6 months of completion of the regimen is considered refractory
    • Relapsed or refractory disease after at least one of the following:

      • At least 2 lines of therapy (including at least one with an anthracycline and anti-CD20 antibody)
      • Autologous stem cell transplant
      • Allogeneic stem cell transplant
  • Patients 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 of 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
  • 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 AND T CELL INFUSION
  • Have a CAR T cell product likely to meet release criteria based on available in-process testing, as reviewed and acknowledged by the individual(s) listed on the protocol's delegation of authority log who are authorized to make this determination
  • Absence of uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with antibiotics, antiviral agents, or antifungal agents
  • Active autoimmune disease requiring ongoing systemic immunosuppressive therapy
  • Negative serum pregnancy test within 2 weeks of 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
  • Treatment with any investigational agent on a different clinical trial within 30 days of lymphodepleting chemotherapy
  • Serum creatinine ≤ 2.5
  • Total bilirubin ≤ 3.0 mg/dL
  • AST and ALT ≤ 5 x the upper limit of normal
  • 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
  • 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
  • Patients must have a Karnofsky performance status of ≥ 60%
  • 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 will not be eligible for leukapheresis and generation of CAR T cell product; 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
  • 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
  • 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 30 days of enrollment
  • Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks of enrollment
  • Previous treatment with CD19-targeted CAR T cells
  • 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)
  • 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

Information from the National Library of Medicine

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): NCT03277729


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Mazyar Shadman    206-667-5467    mshadman@uw.edu   
Principal Investigator: Mazyar Shadman         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mazyar Shadman Fred Hutch/University of Washington Cancer Consortium

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03277729     History of Changes
Other Study ID Numbers: 9738
NCI-2017-01595 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9738 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents