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

Running, not enrolling · Phase 1/Phase 2

Conditions studied: 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, Recurrent Central Nervous System Lymphoma, Refractory Central Nervous System Lymphoma

In brief

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).

Key facts

Study ID: NCT03277729
Run by: Fred Hutchinson Cancer Center
People needed: 53
Starts: 2017-12-05
Expected to finish: 2039-03-01
Last updated by the study team: 2026-06-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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:
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 with large cell lymphoma transformed from indolent lymphomas are eligible if previously treated with anthracycline containing regimen for either the indolent or large cell histology
Patients with central nervous system (CNS) lymphoma need to meet one of the following criteria:
Primary CNS lymphoma:
Progressive disease after 3 cycles or an inadequate response after at least 4 cycles of a high-dose methotrexate (MTX) containing regimen in the opinion of the treating physician, OR
Not eligible for MTX therapy due to commodities or tolerance issues per treating physician OR
Recurrent disease after an initial response to MTX-based treatment
Secondary CNS lymphoma:
An inadequate rtesponse to at least 2 cycles of a MTX containing regimen, OR
Recurrent disease after an initial response to MTX-based treatment
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. For CLL and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (WM) patients, the screening tumor biopsy can we waived for clinical reasons after discussion with the study principal investigator (PI). For patients with CNS lymphoma, a screening tumor biopsy is not required and evidence of CD20 expression can be documented from the original or prior biopsies
Serum creatinine =< 2.5
Total bilirubin =< 3.0 mg/dL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x the upper limit of normal

You may not qualify if…

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
Patients with systemic disease without radiologic evidence of CNS involvement and with isolated CSF involvement detectable by flow cytometry are eligible for enrollment in systemic disease cohorts if neurologically asymptomatic. CSF involvement is not an exclusion for patients enrolled as a primary or secondary CNS lymphoma.
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

Where it is running

Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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