| Eligibility |
Inclusion Criteria:
- PRE-REGISTRATION: Age = 18 years
- PRE-REGISTRATION: Confirmed diagnosis of 1 of the following relapsed or refractory
B-cell hematologic malignancies: chronic lymphocytic leukemia/small lymphocytic
lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal
zone lymphoma (MZL), or large B cell lymphoma (LBCL) including Richter's
transformation from CLL/SLL
- For CD19+ B cell malignancies; relapsed or refractory disease is defined by one
of the following histopathology:
- Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory
disease is defined as:
- Demonstration of progressive or stable disease by positron emission
tomography/computed tomography (PET/CT) or computed tomography (CT) criteria
according to the international workshop on chronic lymphocytic leukemia
(iwCLL) 2018 criteria
- Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology
(including Richter Transformation of CLL); relapsed or refractory disease is
defined as:
- Demonstration of progressive or stable disease by PET/CT or CT criteria as
the best response to the most recent chemotherapy regimen according to the
revised Lugano Response Criteria for Malignant Lymphoma
- PRE-REGISTRATION: Disease Specific prior lines of therapies below:
- For CLL/SLL, patients must have received = two prior lines of therapy, and/or = 6
months of second line prior BTK inhibition (e.g. ibrutinib or other such as
acalabrutinib or zanubrutinib) and must have failed to respond to venetoclax or
be intolerant. Exception: Patients in stable disease (SD) or partial response
(PR) with a known ibrutinib resistance mutation (BTK or phospholipase C?2) may be
included even if on ibrutinib therapy for less than 6 months
- These patients may or may not have received prior antibody directed against
cluster of differentiation 20 (CD20).
- For Follicular Lymphoma, patients must have received = two prior lines of
therapy, including an antibody directed against CD20.
- NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen
receptor T-cell therapy (CART) must have a 100-day washout period.
- For Mantle Cell Lymphoma, patients must have received = two prior lines of
therapy, including an antibody directed against CD20, and a BTK inhibitor.
- NOTE: Prior CD19 directed CART must have a 100-day washout period.
- For Marginal Zone Lymphoma, patients must have received = two prior lines of
therapy, including an antibody directed against CD20.
- NOTE: Prior CD19 directed CART must have a 100-day washout period.
- For Large B cell Lymphoma, patients must have received = two prior lines of
therapy, including an antibody directed against CD20. Prior exposure to CD19
directed CART will be allowed at the discretion of the Principal Investigator.
- NOTE: Prior failed CD19 directed CART must have a 100-day washout period
- For Richter's Transformation, patients must have received =two prior lines of
therapy, including an antibody directed against CD20.
- PRE-REGISTRATION: Measurable disease
- REGISTRATION: Positive BAFFR test
- REGISTRATION: Measurable disease
- REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- REGISTRATION: Hemoglobin = 9.0 g/dL (unless due to documented marrow involvement with
disease) obtained =14 days prior to registration
- REGISTRATION: Absolute neutrophil count (ANC) = 1500/mm^3 (unless due to documented
marrow involvement with disease) obtained =14 days prior to registration
- REGISTRATION: Platelet count =100,000/mm^3 (unless due to documented marrow
involvement with disease) obtained = 14 days prior to registration
- REGISTRATION: Total bilirubin = 1.5 x upper limits of normal (ULN) (Subjects with
Gilbert's Syndrome may be included if their total bilirubin is = 3.0 x ULN and direct
bilirubin = 1.5 x ULN) obtained = 14 days prior to registration
- REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) = 3 x
ULN (= 5 x ULN for patients with liver involvement) obtained = 14 days prior to
registration
- REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR) /activated
partial thromboplastin time (aPTT) = 1.5 x ULN OR if patient is receiving
anticoagulant therapy and INR or aPTT is within target range of therapy obtained = 14
days prior to registration
- Patients on a stable, maintenance regimen of anticoagulant therapy for = 30 days
prior to registration may have PT/INR measurements > 1.5 X ULN if, in the
judgment of the investigator, the patient is suitable for the study
- REGISTRATION: Calculated creatinine clearance =45 ml/min using the Cockcroft-Gault
formula obtained = 14 days prior to registration
- REGISTRATION: Negative pregnancy test done = 7 days prior to registration, for persons
of childbearing potential only. If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required
- REGISTRATION: Provide written informed consent understand and comply with
protocol-required study procedures
- REGISTARTION: Patients must have an ejection fraction (EF) of = 45%
- REGISTRATION: Patients must have pulse ox measurements of > 92% on room air
- REGISTRATION: Willingness to provide mandatory blood specimens for correlative
research
- REGISTRATION: Willing to return to enrolling institution for study follow-up
Exclusion Criteria:
- PRE-REGISTRATION: Prior solid organ transplantation
- PRE-REGISTRATION: Unstable angina, clinically significant arrhythmia, or myocardial
infarction = 6 months of prior to pre-registration, or grade 3 or higher pericardial
effusion at the time of pre-registration
- PRE-REGISTRATION: Prior anti-BAFF-R therapies
- PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy
- PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent = 14
days, prior to pre-registration
- PRE-REGISTRATION: Receiving any other investigational agent which would be considered
as a treatment for the BAFF-R
- PRE-REGISTRATION: Autologous HCT = 60 days prior to pre-registration
- PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not
limited to:
- Previous or concurrent malignancy
- Ongoing or active infection
- Psychiatric illness/social situations
- Dyspnea at rest due to complications of advanced malignancy or other disease that
requires continuous oxygen therapy * Persons of childbearing potential who are
pregnant or breastfeeding
- Life Expectancy of < 6 weeks
- Persons requiring systemic corticosteroids (>10 mg prednisone or equivalent per
day) and/or other immunosuppressive therapy. Patients are allowed to use topical
corticosteroids
- Any other conditions that would limit compliance with study requirements
- PRE-REGISTRATION: Detectable malignant cells from cerebrospinal fluid (CSF) or
magnetic resonance imaging (MRI) indicating brain metastases during screening, or a
history of central nervous system (CNS) involvement by malignancy (CSF or imaging)
with still active disease. Note: Patients with a history of CNS involvement resolving
after treatment and without active disease will be considered eligible if other
inclusion criteria are met
- PRE-REGISTRATION: History of a seizure disorder, major cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
involvement
- PRE-REGISTRATION: Radiation therapy = 14 days prior to pre-registration
- PRE-REGISTRATION: Prior allogeneic hematopoietic stem cell transplant (HCT) in = 6
months prior to pre-registration; patients with active graft versus host disease
(GVHD) will not be eligible regardless of duration from prior allogeneic HCT
- PRE-REGISTRATION: Human immunodeficiency virus (HIV) positive patients
- PRE-REGISTRATION: Subjects with New York Health Association (NYHA) class III or
greater heart failure
- REGISTRATION: Eligible for auto-HCT based on investigator judgement
- REGISTRATION: Presence of active bacterial, viral, or fungal infection that is
uncontrolled, based on investigator judgment
- REGISTRATION: Patients with active hepatitis B or hepatitis C infections are excluded
from the study. Patients who are documented to be HIV positive or proven HIV infection
from testing are ineligible for the study. Infectious disease testing (HIV-1, HIV-2,
hepatitis C virus (HCV) antibody and polymerase chain reaction (PCR), hepatitis B
virus (HBV) surface antigen, HBV surface antibody, HBV core antibody) performed = 45
days prior to registration may be considered for subject eligibility
- REGISTRATION: Previous or concurrent malignancy, except basal cell or squamous cell
skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous
malignancy that was completely resected and has been in remission for = 5 years prior
to registration
- REGISTRATION: Persons of childbearing potential who are pregnant or breastfeeding
- REGISTRATION: Life expectancy of < 6 weeks
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