A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies

Inclusion Criteria

• Men and women of age ≥18 years.
• ECOG performance status of 0, 1, or 2
• Histological diagnosis of CLL/SLL, MCL or MZL (including splenic,nodal and extranodal subtypes) as documented in medical records (pathology reports and slides or blocks should be available for review or additional testing).
• MCL has been previously treated and has relapsed after or progressed during prior therapy. CLL/SLL may have been previously treated or are treatment naïve but now require therapy. MZL has been previously treated and has relapsed after or progressed during at least one prior anti-CD20 -based therapy
• A medically appropriate candidate for ibrutinib treatment (based on the judgement of the clinical investigator).
• Patients who have received prior BTK inhibitor therapy are eligible, unless they demonstrated primary or acquired resistance to a BTK inhibitor or experienced a serious or severe adverse event attributed to BTK inhibitor therapy.
• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 non-biopsied, non-irradiated lesion that measures >1.5 cm in the longest dimension [LD] and ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT] or magnetic resonance imaging [MRI]).
• Current medical need for therapy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
• Completion of all previous therapy (including any Bcl-2 or PI3K inhibitor therapy, surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week (or ≥3 half-lives of the previous drug) before the start of study therapy.
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study therapy (with the exceptions of alopecia, or neurotoxicity [Grade 1 or 2 permitted], or selected laboratory parameters [Grade 1 or Grade 2 permitted with exceptions as noted below]).
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥1.0 × 109/L.
• Platelet count ≥50 × 109/L.
• Hemoglobin ≥8.0 g/dL maintained for ≥1 week from any prior transfusion.
• Adequate hepatic profile:
• Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN).
• Serum aspartate aminotransferase (AST) ≤3 × ULN.
• Serum bilirubin ≤1.5 × ULN unless elevated due to Gilbert syndrome.
• Adequate renal function:
• Estimated creatinine clearance (eClCR) >30 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula [see Appendix 12.2]), or
• Measured creatinine clearance >30 mL/minute (as assessed with a 24-hour urine collection).
• Adequate coagulation profile:
• Prothrombin time (PT) ≤1.5 × ULN.
• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
• Negative viral serology:
• Negative human immunodeficiency virus (HIV) antibody.
• Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) testing.
• Negative hepatitis C virus (HCV) antibody or negative HCV RNA by quantitative PCR.
• For female patients of childbearing potential, a negative urine or serum pregnancy test prior to the start of study therapy.
• For female patients of childbearing potential, willingness to use a highly effective method of contraception from the start of the screening period until ≥3 months after the last dose of cirmtuzumab and ≥1 month after the last dose of ibrutinib, whichever is later. Note: A female patient is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory postmenopausal range and a negative serum or urine beta