Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

Sponsor
Northwestern University (Other)
Overall Status
Terminated
CT.gov ID
NCT01805037
Collaborator
Seagen Inc. (Industry)
20
Enrollment
3
Locations
1
Arm
69.9
Actual Duration (Months)
6.7
Patients Per Site
0.1
Patients Per Site Per Month

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

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: brentuximab vedotin
  • Biological: rituximab
  • Other: laboratory biomarker analysis
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. 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
    1. 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:
  1. 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:
  1. To determine whether and to what extent CD30 expression predicts for response and outcome.

  2. To determine whether and to what extent expression of EBV markers predicts for response and outcome.

  3. 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

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas
Actual Study Start Date :
Mar 5, 2013
Actual Primary Completion Date :
Sep 18, 2017
Actual Study Completion Date :
Dec 31, 2018

Arms and Interventions

ArmIntervention/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:
  • Adcetris
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
  • SGN-35
  • Biological: rituximab
    Given IV
    Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    SiteCityStateCountryPostal Code
    1Northwestern UniversityChicagoIllinoisUnited States60611
    2University of ChicagoChicagoIllinoisUnited States60637
    3Tufts University School of MedicineBostonMassachusettsUnited States02111

    Sponsors and Collaborators

    • Northwestern University
    • Seagen Inc.

    Investigators

    • Principal Investigator: Adam Petrich, MD, Northwestern University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Barbara Pro, MD, Northwestern University
    ClinicalTrials.gov Identifier:
    NCT01805037
    Other Study ID Numbers:
    • NU 12H09
    • NCI-2012-03090
    • STU00072695
    First Posted:
    Mar 5, 2013
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021

    Study Results

    Participant Flow

    Recruitment DetailsThe 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 TitleBrentuximab Vedotin Dose Level -1 (0.8 mg/kg)Brentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionTreatment: 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)
    STARTED020
    Received Dose of Study Drug020
    COMPLETED020
    NOT COMPLETED00
    Period Title: Induction (4 Weeks)
    STARTED06
    Received Dose of Study Drug06
    COMPLETED06
    NOT COMPLETED00
    Period Title: Induction (4 Weeks)
    STARTED020
    Received Dose of Study Drug014
    COMPLETED014
    NOT COMPLETED06
    Period Title: Induction (4 Weeks)
    STARTED014
    Received Dose of Study Drug014
    COMPLETED02
    NOT COMPLETED012
    Period Title: Induction (4 Weeks)
    STARTED020
    COMPLETED014
    NOT COMPLETED06

    Baseline Characteristics

    Arm/Group TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants20
    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

    1. Primary Outcome
    TitleFor Phase I: The Recommended Phase 2 Dose of Brentuximab Vedotin in Combination With Rituximab.
    DescriptionTo 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 FrameThe first 21 days of Induction

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants6
    Number [mg/kg]
    1.2
    2. Primary Outcome
    TitlePhase 1: Number of Dose Limiting Toxicities of Brentuximab Vedotin and Rituximab in Patients With Immunosuppressed Lymphoid Malignancies.
    DescriptionDose 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 FrameThe 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants6
    Number [Grade 3 hyponatremia]
    1
    3. Primary Outcome
    TitlePhase II: Percent of Participants With an Overall Response
    DescriptionOverall 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 FrameEvery 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants20
    Number (95% Confidence Interval) [percent of participants]
    75
    375%
    4. Secondary Outcome
    TitleNumber of Participants With Adverse Events Possibly Related to Study Drug Graded 3, 4, and 5
    DescriptionToxicity, 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 FrameFrom 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants20
    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%
    5. Secondary Outcome
    TitlePercentage of Participants Without Progression (Progression Free Survival (PFS))
    DescriptionStudy 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 Framestart 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants19
    Number (95% Confidence Interval) [percentage of participants]
    75
    375%
    6. Secondary Outcome
    TitlePercentage of Participants Alive at 2 Years (Overall Survival)
    DescriptionOverall 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 FrameFrom 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants19
    Number (90% Confidence Interval) [percent of participants]
    90
    450%
    7. Secondary Outcome
    TitleNumber of Participants With Best Overall Response (BOR)
    DescriptionThe 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 FrameEvery 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants20
    Complete Response
    12
    60%
    Partial Response
    3
    15%
    Stable Disease
    3
    15%
    8. Secondary Outcome
    TitleNumber of Participants With Epstein Barr Virus (EBV) Activation and Number of Participants Without EBV Activation
    DescriptionEBV 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 FrameTime 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants19
    EBV Activation: YES
    1
    5%
    EBV Activation: NO
    18
    90%
    9. Secondary Outcome
    TitleTime to Initiation of Cytotoxic Chemotherapy
    DescriptionTime 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 FrameUp 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants5
    Patient 1
    35
    Patient 2
    147
    Patient 3
    38
    Patient 4
    184
    Patient 5
    66
    10. Secondary Outcome
    TitleNumber of Participants With Graft Rejection vs Without Graft Rejection
    DescriptionGraft 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 FrameFrom 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants19
    Graft Rejection: YES
    1
    5%
    Graft Rejection: NO
    18
    90%
    11. Post-Hoc Outcome
    TitleMedian Time to Best Response
    DescriptionTime 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 FrameFrom 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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 Participants20
    Median (Full Range) [number of days]
    28

    Adverse Events

    Time FrameAdverse 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 TitleBrentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Arm/Group DescriptionInduction: 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
    Total2/20 (10%)
    Serious Adverse Events
    Brentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Affected / at Risk (%)# Events
    Total14/20 (70%)
    Blood and lymphatic system disorders
    Febrile neutropenia1/20 (5%)
    Gastrointestinal disorders
    Abdominal pain1/20 (5%)
    Vomiting1/20 (5%)
    Diarrhea1/20 (5%)
    Typhlitis1/20 (5%)
    General disorders
    Fatigue1/20 (5%)
    Infections and infestations
    Lung Infection2/20 (10%)
    Sepsis2/20 (10%)
    Urinary tract infection1/20 (5%)
    Investigations
    Neutrophil count decreased1/20 (5%)
    Metabolism and nutrition disorders
    Dehydration1/20 (5%)
    Psychiatric disorders
    Confusion1/20 (5%)
    Renal and urinary disorders
    Acute kidney injury2/20 (10%)
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis1/20 (5%)
    Other (Not Including Serious) Adverse Events
    Brentuximb Vedotin Dose Level 1 (1.2 mg/kg)
    Affected / at Risk (%)# Events
    Total20/20 (100%)
    Blood and lymphatic system disorders
    Anemia17/20 (85%)
    Febrile neutropenia1/20 (5%)
    Cardiac disorders
    Atrial flutter1/20 (5%)
    Heart murmur1/20 (5%)
    Chest pain - cardiac1/20 (5%)
    Palpitations1/20 (5%)
    Pericarditis1/20 (5%)
    Sinus tachycardia4/20 (20%)
    Ventricular arrhythmia1/20 (5%)
    Eye disorders
    Blurred vision1/20 (5%)
    Cataract1/20 (5%)
    Eye pain1/20 (5%)
    Floaters1/20 (5%)
    Gastrointestinal disorders
    Abdominal distension1/20 (5%)
    Abdominal pain9/20 (45%)
    Ascites1/20 (5%)
    Bloating2/20 (10%)
    Colitis1/20 (5%)
    Constipation8/20 (40%)
    Diarrhea10/20 (50%)
    Dyspepsia1/20 (5%)
    Dysphagia3/20 (15%)
    Enterocolitis1/20 (5%)
    Flatulence3/20 (15%)
    Gastroesophageal reflux disease2/20 (10%)
    Abnormal satiety1/20 (5%)
    Hemorrhoids1/20 (5%)
    Mucositis oral2/20 (10%)
    Nausea9/20 (45%)
    Oral pain1/20 (5%)
    Typhlitis1/20 (5%)
    Vomiting8/20 (40%)
    General disorders
    Chills2/20 (10%)
    Edema face1/20 (5%)
    Edema limbs7/20 (35%)
    Fatigue10/20 (50%)
    Fever6/20 (30%)
    Night sweats2/20 (10%)
    Infusion related reaction2/20 (10%)
    Injection site reaction1/20 (5%)
    Irritability1/20 (5%)
    Malaise3/20 (15%)
    Non-cardiac chest pain3/20 (15%)
    Pain7/20 (35%)
    Hepatobiliary disorders
    Cholecystitis1/20 (5%)
    Elevated liver enzymes1/20 (5%)
    Drug-induced liver injury1/20 (5%)
    Hepatic steatosis1/20 (5%)
    Immune system disorders
    Allergic reaction1/20 (5%)
    Systemic inflammatory response syndrome1/20 (5%)
    Infections and infestations
    Bronchial infection1/20 (5%)
    Lung Infection1/20 (5%)
    Sepsis4/20 (20%)
    Sinusitis2/20 (10%)
    Upper respiratory infection3/20 (15%)
    Urinary tract infection3/20 (15%)
    Injury, poisoning and procedural complications
    Swollen ankle1/20 (5%)
    Investigations
    Alanine aminotransferase increased8/20 (40%)
    Alkaline phosphatase increased9/20 (45%)
    Aspartate aminotransferase increased11/20 (55%)
    Blood bilirubin increased5/20 (25%)
    Creatinine increased11/20 (55%)
    INR increased3/20 (15%)
    Lipase increased2/20 (10%)
    Lymphocyte count decreased18/20 (90%)
    Neutrophil count decreased10/20 (50%)
    Platelet count decreased8/20 (40%)
    Serum amylase increased4/20 (20%)
    Weight loss2/20 (10%)
    White blood cell decreased10/20 (50%)
    Platelet count increased1/20 (5%)
    Abnormal Blood Urea Nitrogen2/20 (10%)
    Increased Lactate Dehydrogenase1/20 (5%)
    Decreased monocytes1/20 (5%)
    Metabolism and nutrition disorders
    Acidosis1/20 (5%)
    Alkalosis1/20 (5%)
    Anorexia7/20 (35%)
    Dehydration3/20 (15%)
    Hypercalcemia1/20 (5%)
    Hyperglycemia12/20 (60%)
    Hyperkalemia8/20 (40%)
    Hypermagnesemia2/20 (10%)
    Hypernatremia1/20 (5%)
    Hypoalbuminemia11/20 (55%)
    Hypocalcemia11/20 (55%)
    Hypokalemia10/20 (50%)
    Hypomagnesemia5/20 (25%)
    Hyponatremia8/20 (40%)
    Hypophosphatemia3/20 (15%)
    Hypovolemia1/20 (5%)
    Low iron1/20 (5%)
    Lactic Acidosis1/20 (5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia3/20 (15%)
    Back pain4/20 (20%)
    Fibrosis deep connective tissue1/20 (5%)
    Muscle weakness left-sided1/20 (5%)
    Neck pain1/20 (5%)
    Generalized body soreness1/20 (5%)
    Tendonitis1/20 (5%)
    Muscle twinges in legs, abdomen, and chest1/20 (5%)
    Left shoulder pain1/20 (5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Sessile polyp in descending colon1/20 (5%)
    Polyp underneath eye1/20 (5%)
    Nervous system disorders
    Dizziness5/20 (25%)
    Encephalopathy1/20 (5%)
    Headache5/20 (25%)
    Memory impairment1/20 (5%)
    Peripheral motor neuropathy1/20 (5%)
    Peripheral sensory neuropathy7/20 (35%)
    Benign paroxysmal positional vertigo1/20 (5%)
    Difficulty with fine motor skills1/20 (5%)
    Restless leg syndrome1/20 (5%)
    Psychiatric disorders
    Anxiety5/20 (25%)
    Confusion4/20 (20%)
    Depression1/20 (5%)
    Insomnia3/20 (15%)
    Altered mental state1/20 (5%)
    Renal and urinary disorders
    Acute kidney injury7/20 (35%)
    Hematuria1/20 (5%)
    Urinary frequency1/20 (5%)
    Urinary incontinence1/20 (5%)
    Urinary retention1/20 (5%)
    Increase urinary frequency2/20 (10%)
    Malodorous urine1/20 (5%)
    Low glomerular filtration rate1/20 (5%)
    Renal tubulitis1/20 (5%)
    Catheter associated urinary tract infection1/20 (5%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration2/20 (10%)
    Cough6/20 (30%)
    Dyspnea6/20 (30%)
    Hiccups2/20 (10%)
    Nasal congestion2/20 (10%)
    Pleural effusion1/20 (5%)
    Postnasal drip3/20 (15%)
    Pulmonary edema2/20 (10%)
    Sore throat1/20 (5%)
    Mouth sores1/20 (5%)
    Rhinorrhea1/20 (5%)
    Worsening of right lung opacity in CT scan1/20 (5%)
    Pneumonia1/20 (5%)
    Shortness of breath with exertion1/20 (5%)
    Skin and subcutaneous tissue disorders
    Alopecia2/20 (10%)
    Dry skin1/20 (5%)
    Pruritus2/20 (10%)
    Rash maculo-papular1/20 (5%)
    Urticaria1/20 (5%)
    Rash2/20 (10%)
    Erythema1/20 (5%)
    Itching of medial portion of the knees1/20 (5%)
    tender back1/20 (5%)
    redness of left leg1/20 (5%)
    Cellulitis behind ear1/20 (5%)
    Vascular disorders
    Hypertension11/20 (55%)
    Hypotension3/20 (15%)
    Thromboembolic event1/20 (5%)
    Orthostatic hypotension1/20 (5%)

    Limitations/Caveats

    The study did not meet it's accrual goal of 33 patients. The study closed due to lack of funding.

    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/TitleBarbara Pro, MD
    OrganizationNorthwestern University, Feinberg School of Medicine
    Phone312-695-6180
    Emailbarbara.pro@northwestern.edu
    Responsible Party:
    Barbara Pro, MD, Northwestern University
    ClinicalTrials.gov Identifier:
    NCT01805037
    Other Study ID Numbers:
    • NU 12H09
    • NCI-2012-03090
    • STU00072695
    First Posted:
    Mar 5, 2013
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021