Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies
- Conditions
- B-cell Non-Hodgkins LymphomaChronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT02924402
- Lead Sponsor
- Xencor, Inc.
- Brief Summary
The purpose of this study is to determine the safety and tolerability of intravenous (IV) and subcutaneous (SC) administration of XmAb13676 and to determine the maximally tolerated dose (MTD) and/or recommended dose (RD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 154
- Able to provide written informed consent
- Diagnosis of either Non-CLL B cell malignancy
- Ineligible for or have exhausted standard therapeutic options and have relapsed or refractory disease
- ECOG performance status 0-2
- Fertile patients must agree to use highly effective contraception during and for 5 months (male patients) and 8 months (female patients) after last dose of XmAb13676
- Able and willing to complete the entire study
Additional Patient Inclusion Criteria for the DLBCL Cohort (Expansion Phase)
- Histologically confirmed diagnosis (specified by 2016 World Health Organization) of DLBCL or transformed low-grade lymphoma with measurable disease
- Patient must be refractory or have relapsed after 2 or more standard therapeutic options, at least one of which must have included anti-CD20 antibody therapy.
- Not a candidate for or refusing treatment with hematopoietic stem cell transplantation
Additional Patient Inclusion Criteria for the Follicular Lymphoma Cohort (Expansion Phase)
- Diagnosis of follicular lymphoma Grades 1-3a
- Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens.
- Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20 antibodies within 4 weeks, or small molecule or investigational agents within 5 elimination half-lives of the first dose of XmAb13676
- Prior solid organ transplantation
- Failure to recover from Grade 3 or 4 toxicity from previous treatment
- 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) and 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
- Active/uncontrolled autoimmune disease
- Clinically significant cardiac/cardiovascular disease, or pulmonary compromise
- Seizure disorder
- History of stroke with the past 6 mos prior to study entry
- History or evidence of a clinically unstable/uncontrollable disorder, condition or disease other than primary malignancy, that in the opinion of the Investigator would pose a risk to the 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 HBsAb is present or HBV-DNA is negative and patient is receiving Hep B reactivation prophylaxis.
- Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, and 8 months after the last dose of study drug
- Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening
- Live viral vaccine within 2 weeks of the first dose of XmAb13676
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-CLL B Cell Malignancies (Group NHL) Part B XmAb13676 XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion CLL/SLL (Group CLL) Part B XmAb13676 XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion Non-CLL B Cell Malignancies (Group NHL) Part A XmAb13676 XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion CLL/SLL (Group CLL) Part A XmAb13676 XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion Non-CLL B Cell Malignancies (Group NHL) Part C / Expansion XmAb13676 XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion Non-CLL B Cell Malignancies (Group NHL) Part D / Expansion XmAb13676 XmAb13676 administered SC up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
- Primary Outcome Measures
Name Time Method Safety and tolerability as determined by the number of participants with treatment-related adverse events as assessed by CTCAE v4.03 Baseline Day 1 through Day 56 Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb13676 dosing Baseline Day 1 through Day 56
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (23)
The University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Institut Universitaire du Cancer Toulouse Oncopole
🇫🇷Toulouse, France
Chu Montpellier, Hematologie Clinique St. Eloi
🇫🇷Montpellier Cedex 5, France
CLCC Institut Gustave Roussy
🇫🇷Villejuif, France
Moores UC San Diego Cancer Center
🇺🇸La Jolla, California, United States
The Ohio State University Wexner Medical Center and James Cancer Hospital
🇺🇸Columbus, Ohio, United States
UVA Health System, Division of Hematology & Oncology
🇺🇸Charlottesville, Virginia, United States
Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, France
Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
CHU de Nantes
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex, France
Hopital Henri Mondor
🇫🇷Creteil, France
CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie Cellulaire
🇫🇷Pessac, France
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Institut Paoli Calmette Dpt of Oncology/Hematology
🇫🇷Marseille Cedex 9, France
Centre Hospitalier Lyon-Sud, Service d'Hematologie
🇫🇷Pierre-Benite Cedex, France
Centre Henri Becquerel
🇫🇷Rouen, France
Froedtert Hospital and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
University of Michigan
🇺🇸Ann Arbor, Michigan, United States