Xisomab 3G3 for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Receiving Chemotherapy

A Phase II Study of Xisomab 3G3, a Monoclonal Antibody Preventing the Activation of FXI by FXIIa, for the Prophylaxis of Catheter-Associated Thrombosis

This phase II trial studies how well xisomab 3G3 works in preventing catheter-associated blood clots (thrombosis) in patients with cancer receiving chemotherapy. Many patients with cancer develop blood clots from their catheters and can have pain, swelling, and other symptoms. They also often require blood thinners, which can increase the risk of bleeding. Xisomab 3G3 is type of drug called a monoclonal antibody that may prevent blood clots caused by a catheter in patients receiving chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Malignant Solid Neoplasm; Lymphoma; Plasma Cell Myeloma
• Intervention / Treatment: Drug: Xisomab 3G3

Detailed Description

PRIMARY OBJECTIVE I. To determine the efficacy of xisomab as measured by the incidence of catheter-associated thrombosis (CAT) in individuals with a central venous catheter.

SECONDARY OBJECTIVE:

I. To evaluate the safety and tolerability of xisomab 3G3 in cancer patients with a PICC or indwelling catheter.

EXPLORATORY OBJECTIVE:

I. Assessment of drug exposure and catheter occlusions leading to medical intervention.

OUTLINE:

Patients receive xisomab 3G3 intravenously (IV) or via catheter within 48 hours of catheter placement. Patients then receive standard of care chemotherapy 2 days later. After approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.

After completion of study, patients are followed up for 60 days.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed
• In consultation with principal investigator (PI) and treating physician, participant's cancer-directed therapy allows for a 1-day period between administration of study drug and subsequent start of planned cancer-directed therapy
• Individuals with a confirmed solid malignancy that are scheduled to undergo insertion of a PICC line or indwelling central venous catheter as part of planned anticancer therapy per institutional standards
• Must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count > 100 x 10^9/L
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants of childbearing potential are defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal
• Female participants of childbearing potential must agree to use adequate methods of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year without an alternative medical cause
• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy

Exclusion Criteria:

• Actively receiving treatment in another therapeutic clinical trial
• Active acute leukemia (lymphoma and myeloma are allowed)

• At time of enrollment, known contraindication to anticoagulation therapy, including:

  • Clinically significant active bleeding
  • Individual is within 72 hours of major surgery
  • Abnormal baseline coagulation tests, including international normalized ratio (INR) > 1.5, or activated partial thromboplastin time (aPTT) prolonged
  • Abnormal renal function defined by an estimated glomerular filtration rate (eGFR) < 45 mL/min
  • Abnormal hepatic function defined as liver function tests (LFTs) (aspartate aminotransferase [AST], alanine aminotransferase [ALT] or total bilirubin) > 2 x the upper limit of normal or known Child-Pugh class B or C cirrhosis
  • Prior history of intracranial hemorrhage
  • Primary brain tumors or known brain metastasis
  • Major extracranial bleed within the last 6 months where the cause has not been identified or treated
  • Known bleeding diathesis
  • Use of therapeutic anticoagulation or anti-platelet agents for any indication at enrollment
  • At the discretion of the investigator, any other contraindication to anticoagulation therapy
  • Presence of a pediatric-sized PICC line
  • Participant is expected to receive chemotherapy associated with a 15% or higher incidence of grade 3-4 thrombocytopenia within 14 days of receiving study drug
• Preexisting intravenous catheter, or indwelling spinal or epidural catheter, at time of enrollment that is intended to remain for the duration of study. Participants may remain eligible if existing catheter is to be removed before placement of a catheter for cancer directed therapy. Removal of existing catheter should occur at least 24 hours prior to PICC or indwelling catheter insertion
• Previously documented hypersensitivity to either the drug or excipients
• Psychiatric illness/social situations, or any other condition, that in the opinion of the investigator, would limit compliance with study requirements
• Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment
• Participant is allergic to heparin or heparin derivatives
• Participants with a history of venous thromboembolism within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supportive Care (xisomab 3G3); Patients receive xisomab 3G3 IV or via catheter within 48 hours of catheter placement. Patients then receive standard of care chemotherapy 2 days later. After approximately 2 weeks, patients undergo standard of care ultrasound for possible CAT.	Drug: Xisomab 3G3; Given IV or via catheter; Other Names: AB 023; AB-023; AB023; Anti-factor XI Monoclonal Antibody Xisomab 3G3; Anti-FXI Antibody Xisomab 3G3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Catheter-associated Thrombosis (CAT)	The incidence of overall CAT (inclusive of both symptomatic and asymptomatic events) will be assessed and reported with 95% confidence interval.	Up to end of treatment visit (day 18)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Major and Clinically-relevant Bleeding	Bleeding will be defined using the International Society of Thrombosis and Hemostasis definition of major bleeding for clinical investigations of anti-hemostatic medicinal products in nonsurgical patients (i.e., fatal bleeding, critical organ bleeding such as central nervous system bleeding, or bleeding causing a fall in hemoglobin of 20 g/L or more) and clinically relevant non-major bleeding (i.e., bleeding that does not fit the former definition of major bleeding but prompts medical attention). The incidence of major and clinically relevant non-major bleeding, along with 95% confidence interval, will be assessed using the safety analysis set (all patients who are exposed to the single dose of study drug).	Up to end of follow-up (60 days from time of administration)
Incidence of Xisomab 3G3-associated Adverse Events (AEs)	Descriptive statistics of safety will be presented using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 using the safety analysis set (all patients who are exposed to the single dose of study drug). All on-study AEs, treatment-related AEs, serious adverse events (SAEs), and treatment-related SAEs will be tabulated using worst grade per National Cancer Institute (NCI) CTCAE v5.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will be summarized using worst grade NCI CTCAE v5.0 criteria.	Up to end of follow-up (60 days from time of administration)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of Coagulation Measures: Platelet Count	Presented with descriptive statistics.	Up to end of treatment visit (day 18)
Quantification of Coagulation Measures: Prothrombin Time/International Normalized Ratio (PT/INR)	Presented with descriptive statistics.	Up to end of treatment visit (day 18)
Quantification of Coagulation Measures: Activated Partial Thromboplastin Time (aPTT)	Presented with descriptive statistics.	Up to end of treatment visit (day 18)
Xisomab 3G3 Pharmacokinetics	Presented with descriptive statistics.	Up to end of treatment visit (day 18)
Time to Detection of Thrombosis	Will be reported for those (expected few) subjects with symptomatic CAT.	From xisomab 3G3 infusion up to end of treatment visit (day 18)
Time to Clot Symptoms	Will be reported for those (expected few) subjects with symptomatic CAT.	From xisomab 3G3 infusion up to end of treatment visit (day 18)
Proportion of Patients That Had a Catheter Occlusion Requiring Medical Intervention	Results will be presented with descriptive statistics.	Up to end of treatment visit (day 18)

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Oregon Health and Science University
• Investigators: Principal Investigator: Joseph Shatzel, M.D., OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Actual): October 5, 2021
• Study Completion (Actual): November 5, 2021

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: July 7, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 20, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Embolism and Thrombosis; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Thrombosis; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins
• Other Study ID Numbers: STUDY00018976 (Other Identifier: OHSU Knight Cancer Institute); NCI-2020-02554 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01HL151367 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No