Zanubrutinib and CAR T-cell Therapy for the Treatment of Recurrent or Refractory Aggressive B-cell Non-Hodgkin's Lymphoma or Transformed Indolent B-cell Lymphoma
Phase II, Single-Arm, Open-label, Multicenter Study Evaluating the Efficacy of Adjunctive Zanubrutinib and CAR T-Cell Therapy in Aggressive B-Cell Non-Hodgkin's Lymphoma
4 other identifiers
interventional
24
1 country
2
Brief Summary
This phase II trial studies the effect of zanubrutinib and CAR T-cell therapy in treating patients with aggressive B-cell non-Hodgkin's lymphoma or transformed indolent B-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize CAR, a protein on the surface of cancer cells. These CAR-specific T cells may help the body's immune system identify and kill cancer cells. Giving zanubrutinib together with CAR T-cell therapy may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2022
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 4, 2022
CompletedFirst Posted
Study publicly available on registry
January 24, 2022
CompletedStudy Start
First participant enrolled
March 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 9, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 9, 2029
October 16, 2024
October 1, 2024
4.6 years
January 4, 2022
October 14, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Change in 6-month complete response rates
Defined per 2014 Lugano criteria. The proportion of patients with complete response at 6 months will be estimated among evaluable of patients, and reported along with the 95% two-sided Clopper-Pearson confidence interval. A one-sample exact binomial test will be used to compare the 6-month CR rate to the historic control rate of 35%.
At 6 months from initiation of maintenance zanubrutinib treatment
Secondary Outcomes (5)
Conversion rates of partial response (PR) to CR
At day 90, 6, 12, 18, and 24 months from initiation of zanubrutinib maintenance therapy
Overall response rate (ORR)
At day 90, 6, 12, 18, and 24 months from initiation of zanubrutinib maintenance therapy
Progression free survival
From registration until progression/recurrence of lymphoma or death from any cause, assessed at day 90, 6, 12, 18 and 24 months after initiation of zanubrutinib maintenance therapy
Overall survival
From registration until death from any cause, assessed at day 90, 6, 12, 18 and 24 months
Incidence of adverse events
From the time of informed consent until one week post the lead- in treatment period, and then again from day 1 of maintenance treatment phase up to 30 days after treatment discontinuation
Other Outcomes (5)
Quality of life Questionnaire
At screening, 6 and 24 months from initiation of maintenance zanubrutinib treatment
Disease-specific symptoms and/or treatment-related concerns
At screening, 6 and 24 months from initiation of maintenance zanubrutinib treatment
CAR T cell polyfunctionality
Up to 5 years
- +2 more other outcomes
Study Arms (1)
Treatment (zanubrutinib and CAR T-cell therapy)
EXPERIMENTALLEAD- IN PHASE: Patients receive zanubrutinib PO BID for 7-14 days in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive standard of care CAR T-cell therapy IV at 4 weeks. MAINTENANCE PHASE: Patients receive zanubrutinib PO BID on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Ancillary studies
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have a histo-pathologically confirmed diagnosis of an aggressive B-cell non-Hodgkin lymphoma or transformed indolent B-cell lymphoma that is recurrent or refractory to standard therapy and with intent to treat with standard of care CAR T-cell therapy (meeting Food and Drug Administration \[FDA\] approved indications for the respective CAR T-cell construct being used). Standard of care /FDA approved CARTs for this population include axicabtagene ciloleucel, tisagenlecleucel or lisocabtagene maraleucel, any of which may be used for this study and provider dependent. For the purpose of this study, aggressive B-cell NHL histologies should conform to the label indications for the respective CART being utilized. Accordingly, CART eligible histologies include the following groups according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms
- High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
- High-grade B-cell lymphoma, not otherwise specified (NOS)
- Diffuse large B-cell lymphoma (DLBCL), NOS
- Diffuse large B-cell lymphoma (DLBCL), NOS; Germinal center B-cell type
- Diffuse large B-cell lymphoma (DLBCL), NOS; Activated B-cell type
- Large B-cell lymphoma with IRF4 rearrangement
- T-cell/histiocyte-rich large B-cell lymphoma (subtype of DLCBL)
- Primary cutaneous DLBCL, leg type (subtype of DLCBL)
- Epstein-Barr virus (EBV)+ DLBCL, NOS (subtype of DLCBL)
- DLBCL associated with chronic inflammation (subtype of DLCBL)
- Primary mediastinal (thymic) large B-cell lymphoma
- Intravascular large B-cell lymphoma (subtype of DLCBL)
- Transformed indolent B-cell lymphoma; composite lymphomas with aggressive B-cell NHL as outlined above and indolent lymphomas are also allowable if felt to represent transformation
- Patients should have measurable disease per Lugano criteria (2014)
- +23 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents are not eligible
- Patients who require treatment with moderate or strong CYP3A inducers =\< 7 days prior to treatment with zanubrutinib lead-in are not eligible
- Patients requiring systemic treatment with corticosteroids (\> 10mg daily prednisone equivalents) or other immunosuppressive medications including anti-neoplastic therapies =\< 7 days prior to treatment with zanubrutinib lead-in are not eligible
- Please note: Steroids for treatment of lymphoma and/or management of CAR T-cell toxicities are allowed from time of apheresis until 90 days post CAR T-cell therapy. In the event that steroids are deemed necessary for CAR T-cell toxicities after 90 days, this may be done upon discussion with the principal investigator (PI)
- Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on magnetic resonance imaging (MRI) obtained within 4 weeks prior to registration or progressive neurological decline are not eligible
- Patients are not eligible if they have uncontrolled intercurrent illness including, but not limited to
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia deemed clinically significant by the provider
- Or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women and nursing mothers are not eligible
- Patients with human immunodeficiency virus (HIV) are not eligible
- Patients who are unable to swallow oral tablet/gel capsules are not eligible
- Patients who have gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Northwestern University
Chicago, Illinois, 60611, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Reem Karmali, MD
Northwestern University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 4, 2022
First Posted
January 24, 2022
Study Start
March 21, 2022
Primary Completion (Estimated)
October 9, 2026
Study Completion (Estimated)
October 9, 2029
Last Updated
October 16, 2024
Record last verified: 2024-10