Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate how safe and effective the combination of two different drugs (brentuximab vedotin and rituximab) is in patients with certain types of lymphoma. This study is for patients who have a type of lymphoma that expresses a tumor marker called CD30 and/or a type that is associated with the Epstein-Barr virus (EBV-related lymphoma) and who have not yet received any treatment for their cancer, except for dose-reduction or discontinuation (stoppage) of medications used to prevent rejection of transplanted organs (for those patients who have undergone transplantation). This study is investigating the combination of brentuximab vedotin and rituximab as a first treatment for lymphoma patients
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the safety of brentuximab vedotin and rituximab in patients with lymphoid malignancies that are cluster of differentiation (CD) 30 positive (+) and/or Epstein-Barr virus (EBV)+, and to determine the recommended phase 2 dose (RP2D) of the combination. (Phase
-
- To evaluate the efficacy, as measured by response rates, of brentuximab vedotin and rituximab in patients with lymphoid malignancies that are CD30+ and/or EBV+. (Phase II)
SECONDARY OBJECTIVES:
- To further evaluate the frequency and severity of toxicity. (Phase II) II. To further evaluate the clinical efficacy of the combination of brentuximab vedotin and rituximab, as measured by progression free survival (PFS) and overall survival (OS) at one year after the end of treatment. (Phase II) III. To determine the effects of the combination of brentuximab vedotin and rituximab on markers of EBV activation and proliferation. (Phase II) IV. Further evaluate efficacy as measured by time to cytotoxic chemotherapy. (Phase II) V. Further evaluate efficacy as measured by observed rates of graft rejection. (Phase II)
TERTIARY OBJECTIVES:
-
To determine whether and to what extent CD30 expression predicts for response and outcome.
-
To determine whether and to what extent expression of EBV markers predicts for response and outcome.
-
To determine whether changes in serum levels of EBV correlate with response and subsequent loss of response to therapy.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study.
INDUCTION: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes once weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve complete remission (CR) may receive additional optional consolidation therapy identical to induction therapy.
MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 2 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (brentuximab vedotin, rituximab) INDUCTION: Patients receive brentuximab vedotin IV over 30 minutes once weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve CR may receive additional optional consolidation therapy identical to induction therapy. MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Drug: brentuximab vedotin
Given IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- For Phase I: The Recommended Phase 2 Dose of Brentuximab Vedotin in Combination With Rituximab. [The first 21 days of Induction]
To identify the recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD) of brentuximab vedotin in combination with rituximab. The dose limiting toxicity monitoring period for brentuximab vedotin and rituximab is first 21 days (during induction).The RP2D/MTD will be defined as the highest dose of brentuximab vedotin that causes dose limiting toxicities (DLTs) in <2 of 6 patients. The Phase I portion of the study follows a 3+3 design. Brentuximab has two dose levels: Level 1 (starting dose) 1.2 mg/kg IV, and Level -1 (de-escalation dose): 0.8 mg/kg IV. Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
- Phase 1: Number of Dose Limiting Toxicities of Brentuximab Vedotin and Rituximab in Patients With Immunosuppressed Lymphoid Malignancies. [The first 21 days of induction]
Dose limiting toxicities (DLT) will be monitored for Phase 1 patients for the first 21 days of Induction (the DLT monitoring period) to evaluate safety. In general, a non-hematologic DLT is defined as any Grade ≥ 3 toxicity, and a hematologic DLT is defined as any Grade ≥ 4 toxicity, both by CTCAE v4.03 criteria.
- Phase II: Percent of Participants With an Overall Response [Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks]
Overall response will be defined as the detection of Partial Response (PR) or Complete Response (CR) by CT or PET/CT, and/or resolution of marrow-only involvement. Response will be assessed according to the Revised Response Criteria for Malignant Lymphoma (Cheson, et al). CR is defined as a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. A post-treatment residual mass of any size is permitted as long as it is PET negative. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. A PR is defined as At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen.
Secondary Outcome Measures
- Number of Participants With Adverse Events Possibly Related to Study Drug Graded 3, 4, and 5 [From time of treatment to 30 days post discontinuation (range of cycles attempted from induction +/- consolidation, & maintenance = 1-17 cycles) About 1 year Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks]
Toxicity, both frequency and severity, will continue to be measured by monitoring the occurrence of adverse events. Adverse events will be defined as those included in CTCAE v 4.03. AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 (Life-threatening): the patient was at risk of death at the time of the event. Grade 5 (fatal): the event caused death.
- Percentage of Participants Without Progression (Progression Free Survival (PFS)) [start of treatment to time of progression (up to 2 years after treatment discontinuation)]
Study treatment efficacy will be evaluated using PET or CT scan images to determine Progression Free Survival (PFS). PFS is defined as the duration of time from start of treatment to time of progression. Response criteria will be those specified by Cheson, et al as the Revised Response Criteria for Malignant Lymphoma. Progressive Disease (PD) is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size, or at least a 50% increase from nadir in the diameter of any previously involved nodes, or in a single involved node, or the size of other lesions. All patients who have had at least one dose of study treatment will be evaluable for PFS with censoring of patients who are lost to follow-up. PFS will be reported as percentage of participants without progression.
- Percentage of Participants Alive at 2 Years (Overall Survival) [From start of treatment to 2 years post treatment discontinuation]
Overall survival (OS) will be measured from treatment initiation until death from any cause for up to 1 year post-treatment discontinuation. Overall survival is defined as the duration of time from start of treatment to time of death. All patients who have had at least one dose of study treatment will be evaluable for OS. OS will be reported as percentage of participants alive at 2 years post treatment discontinuation, with censoring of patients who are lost to follow-up.
- Number of Participants With Best Overall Response (BOR) [Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks]
The best overall response (BOR) is the best response recorded from the start of the treatment until disease progression/recurrence. Best response assessed by CT or PET/CT according to the Revised Response Criteria for Malignant Lymphoma (Cheson et. al). Responses include Complete Response (CR), Partial Response (PR), and Stable Disease (SD). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. PR: At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. SD: neither CR or PR, or progressive disease (PD). PD: Appearance of new lesion > 1.5 cm in any axis, or at least a 50% increase from nadir in the diameter of any previously involved nodes.
- Number of Participants With Epstein Barr Virus (EBV) Activation and Number of Participants Without EBV Activation [Time from start of study treatment to last dose of study drug (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles, up to 1 year) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks]
EBV activation will be evaluated in all patients who receive at least one dose of study treatment and have an evaluable tissue microarray (TMA) collected at baseline. EBV activation and proliferation will be measured by viral loads from blood collections as measured at time of enrollment and monthly thereafter in all enrolled patients, until completion of study therapy. Epstein Barr Virus (EBV) quantitative PCR is used to an aid in monitoring EBV-related disease. Lab thresholds vary at sites however, labs results are considered either "negative" or "abnormal". Number of participants who experienced EBV activation, i.e an abnormal lab result (YES) and patients who did not experience EBV activation, i.e. a negative lab result (NO) will be reported.
- Time to Initiation of Cytotoxic Chemotherapy [Up to 3 years from treatment discontinuation]
Time to initiation of cytotoxic chemotherapy will be defined as the time elapsed between study treatment initiation, and time of first non-targeted cytotoxic chemotherapy (off study treatment). Time to cytotoxic chemotherapy will be evaluated in all patients who receive at least one dose of study treatment.
- Number of Participants With Graft Rejection vs Without Graft Rejection [From start of treatment to 3 years post treatment discontinuation]
Graft rejection will be defined as any of the following: documentation of new or progressive rejection by tissue biopsy of the graft; re-transplantation due to graft rejection; clinical diagnosis of new or progressive graft rejection, since start of treatment on protocol, as given by the patient's transplant physician. Escalation of intensity of immunosuppression will not, by itself, be considered evidence of graft rejection. Note: patients with clinically active graft rejection will not be excluded from trial enrollment, but will not be considered to have treatment emergent graft rejection unless progression of rejection is documented. Rates of graft rejection will be evaluated in all patients who receive at least one dose of study treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed CD30+ and/or EBV+ lymphoid malignancy; in addition, there must be evidence of CD20 expression (at any level)
-
In cases of post-transplant lymphoproliferative disorder (PTLD) arising in patients who are pharmacologically immunosuppressed, reduction of immunosuppression (RI) must be attempted prior to or in conjunction with enrollment, with the exception of those for whom RI would pose excessive threat of clinically significant graft rejection (as judged by local investigator)
-
No prior chemotherapy or radiotherapy for PTLD or diffuse large B-cell lymphoma (DLBCL), with the exception of corticosteroids for 10 or fewer days at any dose (no washout period required)
-
No prior surgical intervention, unless performed for the sake of tissue diagnosis or on an urgent basis for disease-related threat to life, limb, or organ function
-
Bi-dimensionally measurable disease (at least 1 cm)
-
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
-
Absolute neutrophil count >= 750/mcL
-
Platelets >= 50,000/mcl
-
Total bilirubin =< 2 X institutional upper limit of normal (ULN)
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase [SPGT]) =< 3 X institutional ULN
-
Creatinine =< 2 X institutional ULN
-
NOTE: Patients who do not meet the above criteria because of disease involvement of the organ in question, or because of acute systemic illness due to lymphoma, may enroll with permission of the study Principal Investigator (PI) and approval from the Data Monitoring Committee; this flexibility be allowed due to the heterogeneity of the patient population, the wide range of complications seen in the initial presentation of EBV-related malignancy, and the frequent difficulty encountered in attempting to clearly document that organ dysfunction is the result of an underlying lymphoproliferative disorder
-
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
-
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
-
Has not undergone a hysterectomy or bilateral oophorectomy; or
-
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
-
Patients must be free of any prior malignancies for >= 1 year; NOTE: the exception to this would be currently treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder, or surgically removed melanoma in situ of the skin (stage 0) with histologically confirmed free margins of excision; in addition, it is well-recognized that patients at highest risk for EBV-related lymphoma (ie, those with chronic immunosuppression) are also at high risk for various malignancies, both invasive and non-invasive; therefore, exceptions may also be granted on a case-by-case basis, at the discretion of the PI with approval from the Data Monitoring Committee, for those patients with good clinical control of active malignancy, if the EBV-related lymphoma is considered to be a more immediate threat to the subject's health and/or life
-
Ability to understand and the willingness to sign a written informed consent; all patients must have signed, witnessed informed consent prior to registration
Exclusion Criteria:
-
Chemotherapy (including monoclonal antibodies) or radiotherapy, administered for any condition, within 4 weeks prior to entering the study or incomplete recovery from adverse events due to agents administered more than 4 weeks earlier
-
Ongoing treatment with any other investigational agents
-
Known central nervous system (CNS) involvement of lymphoma
-
History of allergic reactions attributed to compounds of similar chemical or biologic composition to brentuximab vedotin and/or rituximab
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
-
Known human immunodeficiency virus (HIV) infection
-
Known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
-
Clinically active hepatitis A, B, or C infections; NOTE: patients with chronic hepatitis C (HCV) or hepatitis B (HBV) infection may enroll if other laboratory criteria are met; those with HBV surface antigen positivity may enroll only if maintained on appropriate suppressive antiviral therapy, per treating investigator's discretion, for the duration of enrollment in the trial
-
Pregnancy or active nursing of an infant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 2 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 3 | Tufts University School of Medicine | Boston | Massachusetts | United States | 02111 |
Sponsors and Collaborators
- Northwestern University
- Seagen Inc.
Investigators
- Principal Investigator: Adam Petrich, MD, Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.- NU 12H09
- NCI-2012-03090
- STU00072695
Study Results
Participant Flow
| Recruitment Details | The study opened for accrual on March 4th, 2013 with goal of up to 33 patients. The 1st patient started treatment in Phase 1 on March 5th, 2013. 6 patients were accrued in Phase 1. March 26th, 2014 the study opened to Phase II, 14 patients were accrued. October 29th, 2018 the study closed due to lack of funding. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Brentuximab Vedotin Dose Level -1 (0.8 mg/kg) | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|---|
| Arm/Group Description | Treatment: Induction: Brentuximab vedotin 0.8 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks ) Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Period Title: Induction (4 Weeks) | ||
| STARTED | 0 | 20 |
| Received Dose of Study Drug | 0 | 20 |
| COMPLETED | 0 | 20 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Induction (4 Weeks) | ||
| STARTED | 0 | 6 |
| Received Dose of Study Drug | 0 | 6 |
| COMPLETED | 0 | 6 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Induction (4 Weeks) | ||
| STARTED | 0 | 20 |
| Received Dose of Study Drug | 0 | 14 |
| COMPLETED | 0 | 14 |
| NOT COMPLETED | 0 | 6 |
| Period Title: Induction (4 Weeks) | ||
| STARTED | 0 | 14 |
| Received Dose of Study Drug | 0 | 14 |
| COMPLETED | 0 | 2 |
| NOT COMPLETED | 0 | 12 |
| Period Title: Induction (4 Weeks) | ||
| STARTED | 0 | 20 |
| COMPLETED | 0 | 14 |
| NOT COMPLETED | 0 | 6 |
Baseline Characteristics
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Overall Participants | 20 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
9
45%
|
| >=65 years |
11
55%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
40%
|
| Male |
12
60%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
3
15%
|
| Not Hispanic or Latino |
17
85%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
10%
|
| White |
16
80%
|
| More than one race |
1
5%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
20
100%
|
Outcome Measures
| Title | For Phase I: The Recommended Phase 2 Dose of Brentuximab Vedotin in Combination With Rituximab. |
|---|---|
| Description | To identify the recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD) of brentuximab vedotin in combination with rituximab. The dose limiting toxicity monitoring period for brentuximab vedotin and rituximab is first 21 days (during induction).The RP2D/MTD will be defined as the highest dose of brentuximab vedotin that causes dose limiting toxicities (DLTs) in <2 of 6 patients. The Phase I portion of the study follows a 3+3 design. Brentuximab has two dose levels: Level 1 (starting dose) 1.2 mg/kg IV, and Level -1 (de-escalation dose): 0.8 mg/kg IV. Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03. |
| Time Frame | The first 21 days of Induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 6 |
| Number [mg/kg] |
1.2
|
| Title | Phase 1: Number of Dose Limiting Toxicities of Brentuximab Vedotin and Rituximab in Patients With Immunosuppressed Lymphoid Malignancies. |
|---|---|
| Description | Dose limiting toxicities (DLT) will be monitored for Phase 1 patients for the first 21 days of Induction (the DLT monitoring period) to evaluate safety. In general, a non-hematologic DLT is defined as any Grade ≥ 3 toxicity, and a hematologic DLT is defined as any Grade ≥ 4 toxicity, both by CTCAE v4.03 criteria. |
| Time Frame | The first 21 days of induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Six patients in Phase 1 received dose level 1 of brentuximab vedotin (1.2 mg/kg IV). |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 6 |
| Number [Grade 3 hyponatremia] |
1
|
| Title | Phase II: Percent of Participants With an Overall Response |
|---|---|
| Description | Overall response will be defined as the detection of Partial Response (PR) or Complete Response (CR) by CT or PET/CT, and/or resolution of marrow-only involvement. Response will be assessed according to the Revised Response Criteria for Malignant Lymphoma (Cheson, et al). CR is defined as a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. A post-treatment residual mass of any size is permitted as long as it is PET negative. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. A PR is defined as At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. |
| Time Frame | Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 20 |
| Number (95% Confidence Interval) [percent of participants] |
75
375%
|
| Title | Number of Participants With Adverse Events Possibly Related to Study Drug Graded 3, 4, and 5 |
|---|---|
| Description | Toxicity, both frequency and severity, will continue to be measured by monitoring the occurrence of adverse events. Adverse events will be defined as those included in CTCAE v 4.03. AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 (Life-threatening): the patient was at risk of death at the time of the event. Grade 5 (fatal): the event caused death. |
| Time Frame | From time of treatment to 30 days post discontinuation (range of cycles attempted from induction +/- consolidation, & maintenance = 1-17 cycles) About 1 year Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 20 |
| Grade 3 Diarrhea |
1
5%
|
| Grade 4 Hyperbilirubinemia |
1
5%
|
| Grade 3 AST elevation |
2
10%
|
| Grade 4 Lipase elevation |
2
10%
|
| Grade 3 Amylase elevation |
1
5%
|
| Grade 4 Amylase elevation |
1
5%
|
| Grade 4 Typhlitis |
1
5%
|
| Grade 3 Anemia |
2
10%
|
| Grade 3 Febrile Neutropenia |
1
5%
|
| Grade 3 Lymphopenia |
7
35%
|
| Grade 4 Lymphopenia |
2
10%
|
| Grade 4 Neutropenia |
1
5%
|
| Grade 3 Neutropenia |
7
35%
|
| Grade 3 Elevated creatinine |
1
5%
|
| Grade 3 Acute kidney injury |
2
10%
|
| Grade 3 Hypophosphatemia |
1
5%
|
| Grade 3 Peripheral neuropathy |
2
10%
|
| Title | Percentage of Participants Without Progression (Progression Free Survival (PFS)) |
|---|---|
| Description | Study treatment efficacy will be evaluated using PET or CT scan images to determine Progression Free Survival (PFS). PFS is defined as the duration of time from start of treatment to time of progression. Response criteria will be those specified by Cheson, et al as the Revised Response Criteria for Malignant Lymphoma. Progressive Disease (PD) is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size, or at least a 50% increase from nadir in the diameter of any previously involved nodes, or in a single involved node, or the size of other lesions. All patients who have had at least one dose of study treatment will be evaluable for PFS with censoring of patients who are lost to follow-up. PFS will be reported as percentage of participants without progression. |
| Time Frame | start of treatment to time of progression (up to 2 years after treatment discontinuation) |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient was excluded from the analysis because they were lost to follow-up. |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 19 |
| Number (95% Confidence Interval) [percentage of participants] |
75
375%
|
| Title | Percentage of Participants Alive at 2 Years (Overall Survival) |
|---|---|
| Description | Overall survival (OS) will be measured from treatment initiation until death from any cause for up to 1 year post-treatment discontinuation. Overall survival is defined as the duration of time from start of treatment to time of death. All patients who have had at least one dose of study treatment will be evaluable for OS. OS will be reported as percentage of participants alive at 2 years post treatment discontinuation, with censoring of patients who are lost to follow-up. |
| Time Frame | From start of treatment to 2 years post treatment discontinuation |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient was censored from overall survival because they were lost to follow-up. |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 19 |
| Number (90% Confidence Interval) [percent of participants] |
90
450%
|
| Title | Number of Participants With Best Overall Response (BOR) |
|---|---|
| Description | The best overall response (BOR) is the best response recorded from the start of the treatment until disease progression/recurrence. Best response assessed by CT or PET/CT according to the Revised Response Criteria for Malignant Lymphoma (Cheson et. al). Responses include Complete Response (CR), Partial Response (PR), and Stable Disease (SD). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. PR: At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. SD: neither CR or PR, or progressive disease (PD). PD: Appearance of new lesion > 1.5 cm in any axis, or at least a 50% increase from nadir in the diameter of any previously involved nodes. |
| Time Frame | Every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 20 |
| Complete Response |
12
60%
|
| Partial Response |
3
15%
|
| Stable Disease |
3
15%
|
| Title | Number of Participants With Epstein Barr Virus (EBV) Activation and Number of Participants Without EBV Activation |
|---|---|
| Description | EBV activation will be evaluated in all patients who receive at least one dose of study treatment and have an evaluable tissue microarray (TMA) collected at baseline. EBV activation and proliferation will be measured by viral loads from blood collections as measured at time of enrollment and monthly thereafter in all enrolled patients, until completion of study therapy. Epstein Barr Virus (EBV) quantitative PCR is used to an aid in monitoring EBV-related disease. Lab thresholds vary at sites however, labs results are considered either "negative" or "abnormal". Number of participants who experienced EBV activation, i.e an abnormal lab result (YES) and patients who did not experience EBV activation, i.e. a negative lab result (NO) will be reported. |
| Time Frame | Time from start of study treatment to last dose of study drug (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles, up to 1 year) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 1 patient was not evaluable. They withdrew consent before data could be collected. |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 19 |
| EBV Activation: YES |
1
5%
|
| EBV Activation: NO |
18
90%
|
| Title | Time to Initiation of Cytotoxic Chemotherapy |
|---|---|
| Description | Time to initiation of cytotoxic chemotherapy will be defined as the time elapsed between study treatment initiation, and time of first non-targeted cytotoxic chemotherapy (off study treatment). Time to cytotoxic chemotherapy will be evaluated in all patients who receive at least one dose of study treatment. |
| Time Frame | Up to 3 years from treatment discontinuation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Follow-up data for time to initiation of cytotoxic chemotherapy was collected for only 5 patients. That data is reported below. |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 5 |
| Patient 1 |
35
|
| Patient 2 |
147
|
| Patient 3 |
38
|
| Patient 4 |
184
|
| Patient 5 |
66
|
| Title | Number of Participants With Graft Rejection vs Without Graft Rejection |
|---|---|
| Description | Graft rejection will be defined as any of the following: documentation of new or progressive rejection by tissue biopsy of the graft; re-transplantation due to graft rejection; clinical diagnosis of new or progressive graft rejection, since start of treatment on protocol, as given by the patient's transplant physician. Escalation of intensity of immunosuppression will not, by itself, be considered evidence of graft rejection. Note: patients with clinically active graft rejection will not be excluded from trial enrollment, but will not be considered to have treatment emergent graft rejection unless progression of rejection is documented. Rates of graft rejection will be evaluated in all patients who receive at least one dose of study treatment. |
| Time Frame | From start of treatment to 3 years post treatment discontinuation |
Outcome Measure Data
| Analysis Population Description |
|---|
| 1 patient was not evaluable. They withdrew consent before data could be collected. |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 19 |
| Graft Rejection: YES |
1
5%
|
| Graft Rejection: NO |
18
90%
|
| Title | Median Time to Best Response |
|---|---|
| Description | Time to best response = the number of days from treatment initiation to best response (complete response/CR or partial response/PR). Best response assessed by CT or PET/CT according to the Revised Response Criteria for Malignant Lymphoma (Cheson et. al). Responses include Complete Response (CR), Partial Response (PR), and Stable Disease (SD). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms, if present before therapy. If a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. PR: At least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. SD: neither CR or PR, or progressive disease (PD). PD: Appearance of new lesion > 1.5 cm in any axis, or at least a 50% increase from nadir in the diameter of any previously involved nodes. |
| Time Frame | From start of treatment, every 12 weeks for up to 1 year on treatment (Range of cycles attempted from induction, +/- consolidation, + maintenance = 1-17 cycles) Induction = 4 weeks, consolidation = 4 weeks, 1 maintenance cycle = 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) |
|---|---|
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. |
| Measure Participants | 20 |
| Median (Full Range) [number of days] |
28
|
Adverse Events
| Time Frame | Adverse Events (AEs) were collected over a 5 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 30 days post last treatment. Induction = 28 days, consolidation (optional) = 28 days, 1 maintenance cycle = 21 days, with treatment lasting up to 1 year from induction. The range of cycles attempted was 1-17 (including induction +/- consolidation, and maintenance). | |
|---|---|---|
| Adverse Event Reporting Description | Brentuximab vedotin dose level -1 (dose de-escalation level) never opened. All 20 patients received dose level 1 (1.2 mg/kg) of brentuximab vedotin. | |
| Arm/Group Title | Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) | |
| Arm/Group Description | Induction: Brentuximab vedotin 1.2 mg/kg IV infusion over 30 minutes, weekly x 3 (1 cycle = 4 weeks Rituximab 375 mg/m2 IV infusion per standard protocol, once weekly for 4 weeks (1 cycle = 4 weeks) Consolidation (optional): Identical to Induction. Maintenance: Brentuximab vedotin 1.8 mg/kg IV infusion over 30 minutes once every 3 weeks (1 cycle = 3 weeks), for a total of one year from the first induction dose or until progression of disease. Rituximab 375 mg/m2 IV infusion per standard protocol, once every 6 weeks for a total of one year from the first induction dose or until progression of disease. | |
All Cause Mortality |
||
| Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/20 (10%) | |
Serious Adverse Events |
||
| Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/20 (70%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 1/20 (5%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/20 (5%) | |
| Vomiting | 1/20 (5%) | |
| Diarrhea | 1/20 (5%) | |
| Typhlitis | 1/20 (5%) | |
| General disorders | ||
| Fatigue | 1/20 (5%) | |
| Infections and infestations | ||
| Lung Infection | 2/20 (10%) | |
| Sepsis | 2/20 (10%) | |
| Urinary tract infection | 1/20 (5%) | |
| Investigations | ||
| Neutrophil count decreased | 1/20 (5%) | |
| Metabolism and nutrition disorders | ||
| Dehydration | 1/20 (5%) | |
| Psychiatric disorders | ||
| Confusion | 1/20 (5%) | |
| Renal and urinary disorders | ||
| Acute kidney injury | 2/20 (10%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumonitis | 1/20 (5%) | |
Other (Not Including Serious) Adverse Events |
||
| Brentuximb Vedotin Dose Level 1 (1.2 mg/kg) | ||
| Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 17/20 (85%) | |
| Febrile neutropenia | 1/20 (5%) | |
| Cardiac disorders | ||
| Atrial flutter | 1/20 (5%) | |
| Heart murmur | 1/20 (5%) | |
| Chest pain - cardiac | 1/20 (5%) | |
| Palpitations | 1/20 (5%) | |
| Pericarditis | 1/20 (5%) | |
| Sinus tachycardia | 4/20 (20%) | |
| Ventricular arrhythmia | 1/20 (5%) | |
| Eye disorders | ||
| Blurred vision | 1/20 (5%) | |
| Cataract | 1/20 (5%) | |
| Eye pain | 1/20 (5%) | |
| Floaters | 1/20 (5%) | |
| Gastrointestinal disorders | ||
| Abdominal distension | 1/20 (5%) | |
| Abdominal pain | 9/20 (45%) | |
| Ascites | 1/20 (5%) | |
| Bloating | 2/20 (10%) | |
| Colitis | 1/20 (5%) | |
| Constipation | 8/20 (40%) | |
| Diarrhea | 10/20 (50%) | |
| Dyspepsia | 1/20 (5%) | |
| Dysphagia | 3/20 (15%) | |
| Enterocolitis | 1/20 (5%) | |
| Flatulence | 3/20 (15%) | |
| Gastroesophageal reflux disease | 2/20 (10%) | |
| Abnormal satiety | 1/20 (5%) | |
| Hemorrhoids | 1/20 (5%) | |
| Mucositis oral | 2/20 (10%) | |
| Nausea | 9/20 (45%) | |
| Oral pain | 1/20 (5%) | |
| Typhlitis | 1/20 (5%) | |
| Vomiting | 8/20 (40%) | |
| General disorders | ||
| Chills | 2/20 (10%) | |
| Edema face | 1/20 (5%) | |
| Edema limbs | 7/20 (35%) | |
| Fatigue | 10/20 (50%) | |
| Fever | 6/20 (30%) | |
| Night sweats | 2/20 (10%) | |
| Infusion related reaction | 2/20 (10%) | |
| Injection site reaction | 1/20 (5%) | |
| Irritability | 1/20 (5%) | |
| Malaise | 3/20 (15%) | |
| Non-cardiac chest pain | 3/20 (15%) | |
| Pain | 7/20 (35%) | |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/20 (5%) | |
| Elevated liver enzymes | 1/20 (5%) | |
| Drug-induced liver injury | 1/20 (5%) | |
| Hepatic steatosis | 1/20 (5%) | |
| Immune system disorders | ||
| Allergic reaction | 1/20 (5%) | |
| Systemic inflammatory response syndrome | 1/20 (5%) | |
| Infections and infestations | ||
| Bronchial infection | 1/20 (5%) | |
| Lung Infection | 1/20 (5%) | |
| Sepsis | 4/20 (20%) | |
| Sinusitis | 2/20 (10%) | |
| Upper respiratory infection | 3/20 (15%) | |
| Urinary tract infection | 3/20 (15%) | |
| Injury, poisoning and procedural complications | ||
| Swollen ankle | 1/20 (5%) | |
| Investigations | ||
| Alanine aminotransferase increased | 8/20 (40%) | |
| Alkaline phosphatase increased | 9/20 (45%) | |
| Aspartate aminotransferase increased | 11/20 (55%) | |
| Blood bilirubin increased | 5/20 (25%) | |
| Creatinine increased | 11/20 (55%) | |
| INR increased | 3/20 (15%) | |
| Lipase increased | 2/20 (10%) | |
| Lymphocyte count decreased | 18/20 (90%) | |
| Neutrophil count decreased | 10/20 (50%) | |
| Platelet count decreased | 8/20 (40%) | |
| Serum amylase increased | 4/20 (20%) | |
| Weight loss | 2/20 (10%) | |
| White blood cell decreased | 10/20 (50%) | |
| Platelet count increased | 1/20 (5%) | |
| Abnormal Blood Urea Nitrogen | 2/20 (10%) | |
| Increased Lactate Dehydrogenase | 1/20 (5%) | |
| Decreased monocytes | 1/20 (5%) | |
| Metabolism and nutrition disorders | ||
| Acidosis | 1/20 (5%) | |
| Alkalosis | 1/20 (5%) | |
| Anorexia | 7/20 (35%) | |
| Dehydration | 3/20 (15%) | |
| Hypercalcemia | 1/20 (5%) | |
| Hyperglycemia | 12/20 (60%) | |
| Hyperkalemia | 8/20 (40%) | |
| Hypermagnesemia | 2/20 (10%) | |
| Hypernatremia | 1/20 (5%) | |
| Hypoalbuminemia | 11/20 (55%) | |
| Hypocalcemia | 11/20 (55%) | |
| Hypokalemia | 10/20 (50%) | |
| Hypomagnesemia | 5/20 (25%) | |
| Hyponatremia | 8/20 (40%) | |
| Hypophosphatemia | 3/20 (15%) | |
| Hypovolemia | 1/20 (5%) | |
| Low iron | 1/20 (5%) | |
| Lactic Acidosis | 1/20 (5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 3/20 (15%) | |
| Back pain | 4/20 (20%) | |
| Fibrosis deep connective tissue | 1/20 (5%) | |
| Muscle weakness left-sided | 1/20 (5%) | |
| Neck pain | 1/20 (5%) | |
| Generalized body soreness | 1/20 (5%) | |
| Tendonitis | 1/20 (5%) | |
| Muscle twinges in legs, abdomen, and chest | 1/20 (5%) | |
| Left shoulder pain | 1/20 (5%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Sessile polyp in descending colon | 1/20 (5%) | |
| Polyp underneath eye | 1/20 (5%) | |
| Nervous system disorders | ||
| Dizziness | 5/20 (25%) | |
| Encephalopathy | 1/20 (5%) | |
| Headache | 5/20 (25%) | |
| Memory impairment | 1/20 (5%) | |
| Peripheral motor neuropathy | 1/20 (5%) | |
| Peripheral sensory neuropathy | 7/20 (35%) | |
| Benign paroxysmal positional vertigo | 1/20 (5%) | |
| Difficulty with fine motor skills | 1/20 (5%) | |
| Restless leg syndrome | 1/20 (5%) | |
| Psychiatric disorders | ||
| Anxiety | 5/20 (25%) | |
| Confusion | 4/20 (20%) | |
| Depression | 1/20 (5%) | |
| Insomnia | 3/20 (15%) | |
| Altered mental state | 1/20 (5%) | |
| Renal and urinary disorders | ||
| Acute kidney injury | 7/20 (35%) | |
| Hematuria | 1/20 (5%) | |
| Urinary frequency | 1/20 (5%) | |
| Urinary incontinence | 1/20 (5%) | |
| Urinary retention | 1/20 (5%) | |
| Increase urinary frequency | 2/20 (10%) | |
| Malodorous urine | 1/20 (5%) | |
| Low glomerular filtration rate | 1/20 (5%) | |
| Renal tubulitis | 1/20 (5%) | |
| Catheter associated urinary tract infection | 1/20 (5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Aspiration | 2/20 (10%) | |
| Cough | 6/20 (30%) | |
| Dyspnea | 6/20 (30%) | |
| Hiccups | 2/20 (10%) | |
| Nasal congestion | 2/20 (10%) | |
| Pleural effusion | 1/20 (5%) | |
| Postnasal drip | 3/20 (15%) | |
| Pulmonary edema | 2/20 (10%) | |
| Sore throat | 1/20 (5%) | |
| Mouth sores | 1/20 (5%) | |
| Rhinorrhea | 1/20 (5%) | |
| Worsening of right lung opacity in CT scan | 1/20 (5%) | |
| Pneumonia | 1/20 (5%) | |
| Shortness of breath with exertion | 1/20 (5%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 2/20 (10%) | |
| Dry skin | 1/20 (5%) | |
| Pruritus | 2/20 (10%) | |
| Rash maculo-papular | 1/20 (5%) | |
| Urticaria | 1/20 (5%) | |
| Rash | 2/20 (10%) | |
| Erythema | 1/20 (5%) | |
| Itching of medial portion of the knees | 1/20 (5%) | |
| tender back | 1/20 (5%) | |
| redness of left leg | 1/20 (5%) | |
| Cellulitis behind ear | 1/20 (5%) | |
| Vascular disorders | ||
| Hypertension | 11/20 (55%) | |
| Hypotension | 3/20 (15%) | |
| Thromboembolic event | 1/20 (5%) | |
| Orthostatic hypotension | 1/20 (5%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Barbara Pro, MD |
|---|---|
| Organization | Northwestern University, Feinberg School of Medicine |
| Phone | 312-695-6180 |
| barbara.pro@northwestern.edu |
- NU 12H09
- NCI-2012-03090
- STU00072695