Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 1 Multidose Study to Evaluate the Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-Expressing Hematologic Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02924402
• Other study ID #: XmAb13676-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 2016
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Xencor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 270
• Est. completion date: January 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Non-Hodgkins Lymphoma
• Chronic Lymphocytic Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• XmAb13676
Biological

Locations

Country	Name	City	State
France	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	Hopital Henri Mondor	Creteil
France	Institut Paoli Calmette Dpt of Oncology/Hematology	Marseille Cedex 9
France	Chu Montpellier, Hematologie Clinique St. Eloi	Montpellier Cedex 5
France	CHU de Nantes	Nantes
France	Centre Antoine Lacassagne	Nice Cedex
France	CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie Cellulaire	Pessac
France	Centre Hospitalier Lyon-Sud, Service d'Hematologie	Pierre-Benite Cedex
France	Centre Henri Becquerel	Rouen
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
France	CLCC Institut Gustave Roussy	Villejuif
Korea, Republic of	Gachon University Gil Medical Center	Incheon
United Kingdom	Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation Trust	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	UVA Health System, Division of Hematology & Oncology	Charlottesville	Virginia
United States	The University of Chicago Medicine	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center and James Cancer Hospital	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Moores UC San Diego Cancer Center	La Jolla	California
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Xencor, Inc.	ICON Clinical Research

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb13676 dosing		Baseline Day 1 through Day 56