Lymphoma, Malignant Solid Neoplasm, Plasma Cell Myeloma
Conditions
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.
Interventions
DRUGXisomab 3G3
Given IV or via catheter
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Oregon Health and Science University
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Catheter-associated Thrombosis (CAT) | Up to end of treatment visit (day 18) | The incidence of overall CAT (inclusive of both symptomatic and asymptomatic events) will be assessed and reported with 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major and Clinically-relevant Bleeding | Up to end of follow-up (60 days from time of administration) | 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) | Up to end of follow-up (60 days from time of administration) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Xisomab 3G3 Pharmacokinetics | Up to end of treatment visit (day 18) | Presented with descriptive statistics. |
| Time to Detection of Thrombosis | From xisomab 3G3 infusion up to end of treatment visit (day 18) | Will be reported for those (expected few) subjects with symptomatic CAT. |
| Quantification of Coagulation Measures: Platelet Count | Up to end of treatment visit (day 18) | Presented with descriptive statistics. |
| Proportion of Patients That Had a Catheter Occlusion Requiring Medical Intervention | Up to end of treatment visit (day 18) | Results will be presented with descriptive statistics. |
| Time to Clot Symptoms | From xisomab 3G3 infusion up to end of treatment visit (day 18) | Will be reported for those (expected few) subjects with symptomatic CAT. |
| Quantification of Coagulation Measures: Prothrombin Time/International Normalized Ratio (PT/INR) | Up to end of treatment visit (day 18) | Presented with descriptive statistics. |
| Quantification of Coagulation Measures: Activated Partial Thromboplastin Time (aPTT) | Up to end of treatment visit (day 18) | Presented with descriptive statistics. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Xisomab 3G3: Given IV or via catheter | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Supportive Care (Xisomab 3G3) |
|---|---|
| Age, Customized 30-39 years | 1 Participants |
| Age, Customized 40-49 years | 1 Participants |
| Age, Customized 50-59 years | 3 Participants |
| Age, Customized 60-69 years | 2 Participants |
| Age, Customized 70-79 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 9 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
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.
Time frame: Up to end of treatment visit (day 18)
Population: Eight of nine participants underwent screening ultrasound for catheter thrombosis. One patient had their catheter removed prior to screening ultrasound.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Xisomab 3G3) | Incidence of Catheter-associated Thrombosis (CAT) | 1 Participants |
Secondary
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).
Time frame: Up to end of follow-up (60 days from time of administration)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Xisomab 3G3) | Incidence of Major and Clinically-relevant Bleeding | 0 Participants |
Secondary
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.
Time frame: Up to end of follow-up (60 days from time of administration)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Xisomab 3G3) | Incidence of Xisomab 3G3-associated Adverse Events (AEs) | 0 Participants |
Other Pre-specified
Proportion of Patients That Had a Catheter Occlusion Requiring Medical Intervention
Results will be presented with descriptive statistics.
Time frame: Up to end of treatment visit (day 18)
Population: No participants developed catheter occlusion requiring medical intervention prior to the end of treatment visit.
Other Pre-specified
Quantification of Coagulation Measures: Activated Partial Thromboplastin Time (aPTT)
Presented with descriptive statistics.
Time frame: Up to end of treatment visit (day 18)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Xisomab 3G3) | Quantification of Coagulation Measures: Activated Partial Thromboplastin Time (aPTT) | 50.76 Seconds | Standard Deviation 2.81 |
Other Pre-specified
Quantification of Coagulation Measures: Platelet Count
Presented with descriptive statistics.
Time frame: Up to end of treatment visit (day 18)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Xisomab 3G3) | Quantification of Coagulation Measures: Platelet Count | 275 cells*K/mm^3 | Standard Deviation 68 |
Other Pre-specified
Quantification of Coagulation Measures: Prothrombin Time/International Normalized Ratio (PT/INR)
Presented with descriptive statistics.
Time frame: Up to end of treatment visit (day 18)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Xisomab 3G3) | Quantification of Coagulation Measures: Prothrombin Time/International Normalized Ratio (PT/INR) | 1.01 INR | Standard Deviation 0.01 |
Other Pre-specified
Time to Clot Symptoms
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)
Population: No participants developed symptomatic CAT.
Other Pre-specified
Time to Detection of Thrombosis
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)
Population: No participants developed symptomatic CAT.
Other Pre-specified
Xisomab 3G3 Pharmacokinetics
Presented with descriptive statistics.
Time frame: Up to end of treatment visit (day 18)