Clinical Trials

Inclusion Criteria:

• Able to provide written informed consent.
• Adult (age ≥ 18 years).
• Diagnosis of either:
  • Non-CLL B cell malignancy, including (but not limited to) low-grade and/or follicular NHL, diffuse large B cell lymphoma, transformed lymphoma, Burkitt’s or other high-grade lymphoma, mantle cell lymphoma, MALT lymphoma, hairy cell leukemia, and Waldenström’s macroglobulinemia; or
  • CLL/SLL (including Richter’s transformation).
• Patient must be ineligible for or have exhausted standard therapeutic options.
• Last dose of anti-CD20 antibody therapy must have been > 4 weeks before the first dose of XmAb13676.
• ECOG performance status 0-2.
• Not a candidate for or refusing treatment with hematopoietic stem cell transplantation.
• Female patients of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. Women are considered to be of childbearing potential unless it is documented that they are:
  • Over the age of 60; or
  • Postmenopausal by history with no menses for 1 year and confirmed by FSH (using local reference ranges); or
  • Have a history of hysterectomy and/or bilateral oophorectomy; or
  • Have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, transdermal, implantable, or intrauterine), IUDs, vasectomy, or any double-barrier methods (combination of male condom and spermicide with either cap, diaphragm, or sponge).
• Able and willing to complete the entire study according to the study schedule.

 Exclusion Criteria:

• Cytotoxic chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or small molecule or investigational agents within 6 elimination half-lives of the first dose of XmAb13676, except CLL patients who are receiving ibrutinib or acalabrutinib therapy may continue to receive the drug up until the day before treatment with XmAb13676, but may not continue therapy with those drugs once XmAb13676 treatment has begun.
• Prior solid organ transplantation.
• Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to malignant bone marrow involvement).
• Diagnosis of multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia.
• Known intolerance to CD20 monoclonal antibody therapy.
• History of primary central nervous system lymphoma or neoplastic central nervous system disease.
• Platelet count <50 x 10^9/L.
• Absolute neutrophil count < 1.0 x 10^9/L.
• Aspartate aminotransferase (AST) at screening > 3x upper limit of normal (ULN).
• Alanine aminotransferase (ALT) at screening > 3x upper limit of normal (ULN).
• Bilirubin > 1.5 mg/dL (unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made).
• Estimated creatinine clearance < 40 mL/min calculated by the Cockroft Gault or Modification of Diet in Renal Disease (MDRD)2 formulas at screening.
• Active (requiring immunosuppressive medications) or uncontrolled autoimmune disease
• Clinically significant cardiac or cardiovascular disease, such as CHF (e.g., NYHA class III-IV), MI or unstable angina within 6 months prior to study entry, or uncontrolled cardiac arrhythmias.
• Clinically significant pulmonary compromise including, but not limited to, a supplemental oxygen requirement.
• Seizure disorder.
• History of stroke within the past year prior to study entry.
• History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
• Evidence of any serious bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to study entry.
• Positive test for human immunodeficiency virus (HIV) or hepatitis C (HCV) antibodies (unless HCV viral load test by PCR is negative).
• Positive test for HBsAg, or positive test for HBcAb (unless serology is positive due to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if one or more of the following is true:
  • HBsAb is present; or
  • Hepatitis B DNA testing is negative and the patient is receiving hepatitis B reactivation prophylaxis with entecavir, tenofovir, or lamivudine.
• Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the End of Study (EOS) visit.
• Positive urine pregnancy test (i.e., urine human chorionic gonadotropin) at screening.