A PHASE 1 MULTIDOSE STUDY TO EVALUATE THE SAFETY AND TOLERABILITY OF XmAb13676 IN PATIENTS WITH CD20-EXPRESSING HEMATOLOGIC MALIGNANCIES
William G. Wierda
The goal of this clinical research study is to learn about the safety of giving XmAb13676 to patients with certain types of blood, lymph, or bone marrow cancer. Researchers also want to find the highest tolerable dose and/or recommended dose and schedule of XmAb13676. This is the first study using XmAb13676 in humans.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: XmAb 13676
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Xencor, Inc.
Primary: 1. To determine the safety and tolerability profile of XmAb13676 in a) patients with B-cell malignancies excluding chronic lymphocytic leukemia (CLL) and b) patients with CLL or small lymphocytic lymphoma (SLL) 2. To identify the maximum tolerated dose (MTD) and/or recommended dose (RD) and schedule of XmAb13676 administered by weekly intravenous dosing in a) patients with B-cell malignancies excluding CLL and b) patients with CLL/SLL Secondary: 1. To characterize the pharmacokinetics (PK), blood and marrow CD20+ cell pharmacodynamics (PD), and immunogenicity of XmAb13676 2. To preliminarily assess anti-tumor activity of XmAb13676 by response rates, duration of response, and progression-free survival Exploratory: 1. To assess the effects on lymphocyte subsets in peripheral blood and bone marrow by flow cytometry after treatment with XmAb13676 2. To measure changes in T cell activation after XmAb13676 administration by flow cytometry 3. To assess the incidence, timing, and severity of cytokine release syndrome (CRS) by following - CRS-related AEs (incidence and grade of AEs, incidence of SAEs) - Biomarkers of CRS 4. To preliminarily correlate XmAb13676 PD and anti-tumor activity with serum rituximab levels at the time of initial treatment.
IRB Review and Approval Date: 06/13/2017
Recruitment Status: Open
Projected Accrual: 66
1) Able to provide written informed consent
2) Adult (age >/= 18 years)
3) Diagnosis of either (a) 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 (b) CLL/SLL (including Richter’s transformation)
4) Patient must be ineligible for or have exhausted standard therapeutic options
5) Last dose of anti-CD20 antibody therapy must have been > 4 weeks before the first dose of XmAb13676
6) ECOG performance status 0-2
7) Not a candidate for or refusing treatment with hematopoietic stem cell transplantation
8) 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).
9) Able and willing to complete the entire study according to the study schedule
1) 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
2) Prior allogeneic stem cell or solid organ transplantation
3) Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to malignant bone marrow involvement)
4) Diagnosis of multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia
5) Known intolerance to CD20 monoclonal antibody therapy
6) History of primary central nervous system lymphoma or neoplastic central nervous system disease
7) Platelet count < 50 x 10(9)/L
8) Absolute neutrophil count < 1.0 x 10(9)/L
9) Aspartate aminotransferase (AST) at screening >3x upper limit of normal (ULN)
10) Alanine aminotransferase (ALT) at screening >3x ULN
11) Bilirubin > 1.5 mg/dL (unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made)
12) Estimated creatinine clearance <50 mL/min calculated by the Cockroft Gault or Modification of Diet in Renal Disease (MDRD)^2 formulas at screening
13) Active/uncontrolled autoimmune disease
14) 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
15) Clinically significant pulmonary compromise, including but not limited to a supplemental oxygen requirement
16) Seizure disorder
17) History of stroke within the past year prior to study entry
18) 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.
19) Evidence of any serious bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to study entry
20) Positive test for human immunodeficiency virus (HIV) or hepatitis C antibodies (unless a HCV viral load test by PCR is negative)
21) 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 HBsAb is present.
22) Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the End of Study (EOS) visit.
23) Positive urine pregnancy test (i.e., urine human chorionic gonadotropin) at screening.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
William G. Wierda
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