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

Primary Purpose

Lymphoma, Malignant Solid Neoplasm, Plasma Cell Myeloma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Xisomab 3G3
Sponsored by
OHSU Knight Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • OHSU Knight Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive Care (xisomab 3G3)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.

Full Information

First Posted
June 25, 2020
Last Updated
October 10, 2022
Sponsor
OHSU Knight Cancer Institute
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Oregon Health and Science University
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1. Study Identification

Unique Protocol Identification Number
NCT04465760
Brief Title
Xisomab 3G3 for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Receiving Chemotherapy
Official Title
A Phase II Study of Xisomab 3G3, a Monoclonal Antibody Preventing the Activation of FXI by FXIIa, for the Prophylaxis of Catheter-Associated Thrombosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 25, 2021 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Oregon Health and Science University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Malignant Solid Neoplasm, Plasma Cell Myeloma

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Supportive Care (xisomab 3G3)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Xisomab 3G3
Other Intervention Name(s)
AB 023, AB-023, AB023, Anti-factor XI Monoclonal Antibody Xisomab 3G3, Anti-FXI Antibody Xisomab 3G3
Intervention Description
Given IV or via catheter
Primary Outcome Measure Information:
Title
Incidence of catheter-associated thrombosis (CAT)
Description
The incidence of overall CAT (inclusive of both symptomatic and asymptomatic events) will be assessed and reported with 95% confidence interval.
Time Frame
Up to end of treatment visit (day 18)
Secondary Outcome Measure Information:
Title
Incidence of major and clinically-relevant bleeding
Description
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).
Time Frame
Up to end of follow-up (60 days from time of administration)
Title
Incidence of xisomab 3G3-associated adverse events (AEs)
Description
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.
Time Frame
Up to end of follow-up (60 days from time of administration)
Other Pre-specified Outcome Measures:
Title
Quantification of coagulation measures: platelet count
Description
Presented with descriptive statistics.
Time Frame
Up to end of treatment visit (day 18)
Title
Quantification of coagulation measures: Prothrombin time/international normalized ratio (PT/INR)
Description
Presented with descriptive statistics.
Time Frame
Up to end of treatment visit (day 18)
Title
Quantification of coagulation measures: Activated partial thromboplastin time (aPTT)
Description
Presented with descriptive statistics.
Time Frame
Up to end of treatment visit (day 18)
Title
Xisomab 3G3 pharmacokinetics
Description
Presented with descriptive statistics.
Time Frame
Up to end of treatment visit (day 18)
Title
Time to detection of thrombosis
Description
Will be reported for those (expected few) subjects with symptomatic CAT.
Time Frame
From xisomab 3G3 infusion up to end of treatment visit (day 18)
Title
Time to clot symptoms
Description
Will be reported for those (expected few) subjects with symptomatic CAT.
Time Frame
From xisomab 3G3 infusion up to end of treatment visit (day 18)
Title
Proportion of patients that had a catheter occlusion requiring medical intervention
Description
Results will be presented with descriptive statistics.
Time Frame
Up to end of treatment visit (day 18)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Shatzel, M.D.
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph J. Shatzel, M.D.
Phone
503-494-6594
Email
shatzel@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Joseph J. Shatzel, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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