| Eligibility |
Inclusion Criteria:
1. Histologically confirmed B-cell lymphoma, relapsed to or refractory after at least one
prior standard therapy. For subjects with aggressive lymphoma: those who are
non-candidates for high-dose therapy or autologous stem cell transplant. Refractory is
defined as disease progression during or within 6 months of the most recent prior
therapy, while relapsed is defined as disease progression greater than 6 months after
the most recent prior therapy.
2. Measurable disease defined as at least 1 measurable disease lesion = 1.5 cm in at
least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no
prior radiation therapy, or in an area that was previously irradiated that has
documented progression.
3. Be able to provide a core or excisional lymph node biopsy for biomarker analysis from
an archival or newly obtained biopsy at Screening.
4. Adequate organ function defined as:
1. Absolute neutrophil count (ANC) > 1,000/µL and platelet count > 75,000/µL.
Platelet requirements cannot be met by use of recent transfusion (within 30 days
of study treatment initiation [Cycle 1 Day 1]). Growth factor support (e.g.
G-CSF) is not allowed within 2 weeks prior to treatment initiation.
2. Total bilirubin = 1.5 times the ULN, or direct bilirubin = ULN for subjects with
total bilirubin > 1.5 ULN.
3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN
if no liver involvement or = 5 x the ULN if known liver involvement.
4. Calculated creatinine (Cr) clearance (CL) > 30 mL/min (as calculated by the
Cockcroft-Gault or MDRD formula, 24-hour urine Cr CL also acceptable).
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
6. Male or female = 18 years of age.
7. Female subjects who are not of child-bearing potential, and female subjects of
child-bearing potential who have a negative serum pregnancy test within 3 days prior
to Cycle 1, Day 1. Female subjects of child-bearing potential, and male partners must
consent to use a medically acceptable method of contraception throughout the study
period and for 4 months after the last administration of ublituximab and 30 days after
last administration of TG-1801. Men of reproductive potential may not participate
unless they agree to use medically acceptable contraception.
8. Willingness and ability to comply with trial and follow-up procedures and provide
written informed consent.
Exclusion Criteria:
1. Prior therapy with any agent blocking the CD47/SIRPa pathway or any previous CD19
targeting therapy, including but not limited to: antibodies, fragments, bispecific
bodies, or chimeric antigen receptor (CAR) T-cells.
2. Subjects receiving cancer therapy (i.e. chemotherapy, radiation therapy,
immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization)
or any investigational drug within 21 days of Day 1 of Cycle 1 (42 days for prior
mitomycin C or a nitrosourea).
a. Corticosteroid therapy started at least 7 days prior to Cycle 1 Day 1 (prednisone =
10 mg daily or equivalent) is allowed as clinically warranted. Topical or inhaled
corticosteroids are permitted.
3. Prior autologous stem cell transplant within 6 months. Prior allogeneic hematologic
stem cell transplant within 1 year and excluded if there is active graft versus host
disease.
4. Subjects who have not recovered (= Grade 1 or at baseline) from adverse events due to
previous therapy, except for alopecia and Grade 2 neuropathy due to previous cancer
therapy.
Note: Toxicity that has not recovered to = Grade 1 is allowed if it meets the
inclusion requirements for laboratory parameters defined above.
5. Any severe or uncontrolled illness or other conditions that could affect their
participation in the study including, but not limited to:
1. Symptomatic, or history of documented congestive heart failure (NY Heart
Association functional classification III-IV).
2. Myocardial infarction within 6 months of enrollment.
3. Poorly controlled or clinically significant atherosclerotic vascular disease
including cerebrovascular accident, transient ischemic attack, angioplasty,
cardiac/vascular stenting within 6 months of enrollment, angina not well
controlled by medication.
4. Ongoing or active infection, except localized fungal infection of skin or nails.
6. Known active Hepatitis B (e.g. HBsAg reactive), Hepatitis C (e.g. HCV RNA
[qualitative] is detected), cytomegalovirus (CMV DNA by PCR), or known history of HIV.
7. Malignancy within 2 years of study enrollment except for adequately treated basal or
squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast,
superficial bladder cancer, or localized prostate cancer.
8. Known clinically active CNS involvement.
9. History of anaphylaxis or severe allergy to a monoclonal antibody; or known or
suspected hypersensitivity to the excipients contained in the study drug formulation.
10. Lactating or pregnant.
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