Clinical trial NCT02924402: Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies
Official title: A Phase 1 Multidose Study to Evaluate the Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-Expressing Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Non-Hodgkins Lymphoma
Chronic Lymphocytic Leukemia
Keywords: NHL
B-cell Prolymphocytic Leukemia
Transformed Lymphoma
Burkitt's Lymphoma
Mantle Cell Lymphoma
Hairy Cell Leukemia
Splenic Marginal Zone Lymphoma
Waldenstrom's Macroglobulinemia
Variant Hairy Cell Leukemia
Splenic B-cell Lymphoma/Leukemia
Lymphoplasmacytic Lymphoma
Extranodal Marginal Zone Lymphoma (MALT)
MALT Lymphoma
Nodal Marginal Zone Lymphoma
Follicular Lymphoma
In Situ Follicular Neoplasia
Duodenal-type Follicular Lymphoma
Large B-cell Lymphoma with IRF4 rearrangement
Primary Cutaneous Follicle Center Lymphoma
Diffuse Large B-cell Lymphoma
DLBCL
T-cell/Histiocyte-Rich Large B-cell Lymphoma
Primary Cutaneous DLBCL, leg type
EBV-positive DLBCL, NOS
EBV-positive Mucocutaneous Ulcer
DLBCL Associated with Chronic Inflammation
Lymphomatoid Granulomatosis
Primary Mediastinal (Thymic) Large B-cell Lymphoma
Intravascular Large B-cell Lymphoma
ALK+ Large B-cell Lymphoma
Plasmablastic Lymphoma
Primary Effusion Lymphoma
HHV8+ DLBCL
Burkitt-like Lymphoma with 11q Aberration
High-grade B-cell Lymphoma
B-cell Lymphoma, unclassifiable
Post-transplant Lymphoproliferative Disorder
PTLD
SLL
High-grade Lymphoma
Richter's Transformation
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2016-10-05
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will enroll two parallel disease groups in escalation: patients with non-CLL B cell malignancies and patients with CLL/SLL/Richter's Transformation. In expansion it will enroll DLBCL and FL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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)

1. Histologically confirmed diagnosis (specified by 2016 World Health Organization) of DLBCL or transformed low-grade lymphoma with measurable disease
2. 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.
3. Not a candidate for or refusing treatment with hematopoietic stem cell transplantation

Additional Patient Inclusion Criteria for the Follicular Lymphoma Cohort (Expansion Phase)

1. Diagnosis of follicular lymphoma Grades 1-3a
2. Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety and tolerability as determined by the number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: Baseline Day 1 through Day 56
measure: Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb13676 dosing
timeFrame: Baseline Day 1 through Day 56
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center and James Cancer Hospital
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: UVA Health System, Division of Hematology & Oncology
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and Medical College of Wisconsin
state: Wisconsin
city: Bordeaux
country: France
facility: Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmette Dpt of Oncology/Hematology
city: Montpellier Cedex 5
country: France
facility: Chu Montpellier, Hematologie Clinique St. Eloi
city: Nantes
country: France
facility: CHU de Nantes
city: Nice Cedex
country: France
facility: Centre Antoine Lacassagne
city: Pessac
country: France
facility: CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie Cellulaire
city: Pierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon-Sud, Service d'Hematologie
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Villejuif
country: France
facility: CLCC Institut Gustave Roussy
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: London
country: United Kingdom
facility: Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Executive Medical Director, Clinical Development, Xencor, Inc.
name: Chet Bohac, PharmD, MD, MSc
role: STUDY_DIRECTOR
References: