BV-ICE: Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

Sponsor
University of Washington (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02227199
Collaborator
National Cancer Institute (NCI) (NIH), Seagen Inc. (Industry)
45
1
3
124.1
0.4

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide chemotherapy regimen may kill more cancer cells.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine maximally tolerated dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin and etoposide chemotherapy in patients with relapsed or refractory Hodgkin lymphoma.

  2. To gain a preliminary assessment of the efficacy of the above regimen.

SECONDARY OBJECTIVES:
  1. To determine the safety and toxicity of the above regimen.

  2. To determine the ability to proceed to peripheral blood stem cell collection following the above regimen (the impact of above regimen on stem cell reserve).

  3. To assess the impact of this regimen on biomarkers from the microenvironment in Hodgkin lymphoma tumors.

OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study.

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) may undergo peripheral blood stem cell (PBSC) mobilization following the 2nd course of study therapy at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Trial of Brentuximab Vedotin (BV), Ifosfamide (I), Carboplatin (C), and Etoposide (E) for Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE)
Actual Study Start Date :
Oct 10, 2014
Actual Primary Completion Date :
Mar 30, 2020
Anticipated Study Completion Date :
Feb 10, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)

Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

Drug: Brentuximab Vedotin
Given IV
Other Names:
  • ADC SGN-35
  • Adcetris
  • Anti-CD30 Antibody-Drug Conjugate SGN-35
  • Anti-CD30 Monoclonal Antibody-MMAE SGN-35
  • Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
  • cAC10-vcMMAE
  • SGN-35
  • Drug: Carboplatin
    Given IV
    Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)

    Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

    Drug: Brentuximab Vedotin
    Given IV
    Other Names:
  • ADC SGN-35
  • Adcetris
  • Anti-CD30 Antibody-Drug Conjugate SGN-35
  • Anti-CD30 Monoclonal Antibody-MMAE SGN-35
  • Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
  • cAC10-vcMMAE
  • SGN-35
  • Drug: Carboplatin
    Given IV
    Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Experimental: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)

    Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.

    Drug: Brentuximab Vedotin
    Given IV
    Other Names:
  • ADC SGN-35
  • Adcetris
  • Anti-CD30 Antibody-Drug Conjugate SGN-35
  • Anti-CD30 Monoclonal Antibody-MMAE SGN-35
  • Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
  • cAC10-vcMMAE
  • SGN-35
  • Drug: Carboplatin
    Given IV
    Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy [Up to 28 days following the second course of chemotherapy, approximately 70 days]

      Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

    2. Percentage of Patients That Achieve a Complete Remission Following Study Treatment [3 weeks following the completion of chemotherapy]

    Secondary Outcome Measures

    1. 2 Year Overall Survival [Up to 2 years from initiation of study therapy.]

    2. 2 Year Progression-free Survival [Up to 2 years from initiation of therapy.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have primary refractory or first relapse of cluster of differentiation 30 (CD30)+ Hodgkin lymphoma

    • Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm; further, at least 1 of these lesions must be positive by positron emission tomography (PET) scan (i.e., Deauville score of 4 or more); Note: CT scans remain the standard for evaluation of nodal disease

    • Patients must have a CT of chest, abdomen, and pelvis with PET within 28 days of enrollment; patients with evidence of lymphadenopathy in the neck must have a dedicated CT of neck

    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (performance status of 2 will be allowed if poor performance status is thought to be directly secondary to patient's Hodgkin lymphoma [HL])

    • Absolute neutrophil count (ANC) >= 1,500/uL, performed within 28 days prior to registration

    • Platelets >= 100,000/uL (without transfusion or growth factor support), performed within 28 days prior to registration

    • Serum creatinine < 1.5 mg/dl or creatinine clearance (CrCl) > 60 mL/min, performed within 28 days prior to registration

    • Total bilirubin < 2 times upper limit of normal (unless due to Gilbert's syndrome), performed within 28 days prior to registration

    • Aspartate aminotransferase (AST) < 2.5 times upper limit of normal, performed within 28 days prior to registration

    • All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines

    • Patients must be anticipated to complete 2 cycles of chemotherapy

    Exclusion Criteria:
    • Patients known to be positive for human immunodeficiency virus (HIV)

    • Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

    • Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol chair or co-chair

    • Patients with known allergy, intolerance, or resistance (i.e., remission duration less than 6 months or lack of response) to ifosfamide, carboplatin, or etoposide

    • Patients with evidence of active central nervous system lymphoma

    • Patients with prior receipt of brentuximab vedotin

    • Patients with peripheral neuropathy of > grade 1

    • Patients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled arrhythmia); if the patient's cardiac history is questionable, a measurement of left ventricular ejection fraction should be obtained within 42 days prior to registration; patients with left ventricular ejection fraction < 50% are not eligible

    • Prior failed (< 5 x 10^6 CD34/kg) peripheral blood stem cell (PBSC) collection

    • Patients who had pelvic radiation within 12 months

    • Previous chemotherapy/immunotherapy within 3 weeks before study entry

    • Concurrent use of other anti-cancer agents or experimental treatments

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • University of Washington
    • National Cancer Institute (NCI)
    • Seagen Inc.

    Investigators

    • Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Ajay Gopal, Professor, Department of Medicine, Division of Oncology, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02227199
    Other Study ID Numbers:
    • 9111
    • NCI-2014-01782
    • 9111
    • P30CA015704
    • RG1714038
    First Posted:
    Aug 28, 2014
    Last Update Posted:
    Jun 30, 2022
    Last Verified:
    Jun 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 2: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab Vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies
    Period Title: Overall Study
    STARTED 3 3 39
    COMPLETED 3 3 35
    NOT COMPLETED 0 0 4

    Baseline Characteristics

    Arm/Group Title Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Total
    Arm/Group Description Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Total of all reporting groups
    Overall Participants 3 3 39 45
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    100%
    3
    100%
    39
    100%
    45
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    0
    0%
    27
    69.2%
    29
    64.4%
    Male
    1
    33.3%
    3
    100%
    12
    30.8%
    16
    35.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    4
    10.3%
    4
    8.9%
    Not Hispanic or Latino
    3
    100%
    3
    100%
    35
    89.7%
    41
    91.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    4
    10.3%
    4
    8.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    2
    5.1%
    2
    4.4%
    White
    3
    100%
    3
    100%
    32
    82.1%
    38
    84.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    2.6%
    1
    2.2%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    39
    100%
    45
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
    Description Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
    Time Frame Up to 28 days following the second course of chemotherapy, approximately 70 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Brentuximab, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab vedotin IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 6
    Number [mg/kg]
    1.5
    2. Primary Outcome
    Title Percentage of Patients That Achieve a Complete Remission Following Study Treatment
    Description
    Time Frame 3 weeks following the completion of chemotherapy

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab Vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 3 3 39
    Count of Participants [Participants]
    3
    100%
    3
    100%
    26
    66.7%
    3. Secondary Outcome
    Title 2 Year Overall Survival
    Description
    Time Frame Up to 2 years from initiation of study therapy.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 3 3 39
    Count of Participants [Participants]
    3
    100%
    3
    100%
    37
    94.9%
    4. Secondary Outcome
    Title 2 Year Progression-free Survival
    Description
    Time Frame Up to 2 years from initiation of therapy.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies
    Measure Participants 3 3 39
    Count of Participants [Participants]
    2
    66.7%
    3
    100%
    33
    84.6%

    Adverse Events

    Time Frame Adverse events were collected starting after the first dose of study treatment and collected through 30 days after the last dose of study drug, or until the patient receives an alternative anti-cancer therapy, whichever date comes first, approximately 60 days.
    Adverse Event Reporting Description
    Arm/Group Title Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Arm/Group Description Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician. Brentuximab Vedotin: Given IV Carboplatin: Given IV Etoposide: Given IV Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
    All Cause Mortality
    Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 2/39 (5.1%)
    Serious Adverse Events
    Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 1/3 (33.3%) 11/39 (28.2%)
    Cardiac disorders
    Tachycardia 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    Endocrine disorders
    Diabetic Ketoacidosis 0/3 (0%) 0 0/3 (0%) 0 2/39 (5.1%) 2
    Gastrointestinal disorders
    Gastroenteritis 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    General disorders
    Fever 0/3 (0%) 0 1/3 (33.3%) 1 3/39 (7.7%) 3
    Neutropenic Fever 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Infections and infestations
    Septic Shock /3 (NaN) 0/3 (0%) 0 1/39 (2.6%) 1
    Sepsis 0/3 (0%) 0 1/3 (33.3%) 1 4/39 (10.3%) 4
    Investigations
    Elevated Lactate 0/3 (0%) 0 0/3 (0%) 0 2/39 (5.1%) 2
    Metabolism and nutrition disorders
    Hypokalemia 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    Hyperglycemia 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    Skin and subcutaneous tissue disorders
    Sweet Syndrome 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    Erythematous Rash 0/3 (0%) 0 1/3 (33.3%) 1 1/39 (2.6%) 1
    Vascular disorders
    Hypotension 0/3 (0%) 0 1/3 (33.3%) 1 2/39 (5.1%) 2
    Pulmonary Embolism 0/3 (0%) 0 0/3 (0%) 0 1/39 (2.6%) 1
    Other (Not Including Serious) Adverse Events
    Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide) Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 39/39 (100%)
    Blood and lymphatic system disorders
    Anemia 1/3 (33.3%) 2 1/3 (33.3%) 1 8/39 (20.5%) 10
    Leukocytosis 1/3 (33.3%) 1 1/3 (33.3%) 1 4/39 (10.3%) 4
    Cardiac disorders
    Tachycardia 2/3 (66.7%) 2 2/3 (66.7%) 2 11/39 (28.2%) 11
    Palpitations 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Hypotension 0/3 (0%) 0 0/3 (0%) 0 4/39 (10.3%) 4
    Eye disorders
    Blurred Vision 0/3 (0%) 0 1/3 (33.3%) 1 2/39 (5.1%) 2
    Gastrointestinal disorders
    Abdominal Pain 2/3 (66.7%) 2 0/3 (0%) 0 11/39 (28.2%) 13
    Constipation 2/3 (66.7%) 2 3/3 (100%) 4 18/39 (46.2%) 19
    Diarrhea 0/3 (0%) 0 2/3 (66.7%) 2 10/39 (25.6%) 15
    Vomiting 0/3 (0%) 0 2/3 (66.7%) 3 18/39 (46.2%) 23
    Nausea 2/3 (66.7%) 3 3/3 (100%) 3 29/39 (74.4%) 40
    Dry Mouth 0/3 (0%) 0 2/3 (66.7%) 2 2/39 (5.1%) 2
    Gastroesophageal Reflux Disease 0/3 (0%) 0 0/3 (0%) 0 12/39 (30.8%) 12
    Mucositis Oral 0/3 (0%) 0 2/3 (66.7%) 2 2/39 (5.1%) 2
    General disorders
    Non-cardiac chest pain 0/3 (0%) 0 1/3 (33.3%) 2 6/39 (15.4%) 7
    Infusion related reaction 0/3 (0%) 0 1/3 (33.3%) 1 2/39 (5.1%) 2
    Fatigue 2/3 (66.7%) 4 3/3 (100%) 3 16/39 (41%) 19
    Fever 1/3 (33.3%) 1 2/3 (66.7%) 2 4/39 (10.3%) 6
    Hiccups 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Night Sweats 0/3 (0%) 0 0/3 (0%) 0 5/39 (12.8%) 5
    Pain 0/3 (0%) 0 0/3 (0%) 0 7/39 (17.9%) 8
    Edema Limbs 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Pain at Hickman Site 2/3 (66.7%) 2 1/3 (33.3%) 1 4/39 (10.3%) 4
    Flushing 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Infections and infestations
    Upper Respiratory Infection 0/3 (0%) 0 2/3 (66.7%) 4 6/39 (15.4%) 6
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 0/3 (0%) 0 12/39 (30.8%) 30
    Aspartate aminotransferase increased 0/3 (0%) 0 0/3 (0%) 0 10/39 (25.6%) 17
    Platelet Count Decreased 2/3 (66.7%) 3 1/3 (33.3%) 3 5/39 (12.8%) 8
    Weight Loss 0/3 (0%) 0 0/3 (0%) 0 3/39 (7.7%) 3
    Neutrophil Count Decreased 1/3 (33.3%) 1 1/3 (33.3%) 2 1/39 (2.6%) 1
    Metabolism and nutrition disorders
    Anorexia 2/3 (66.7%) 2 3/3 (100%) 3 6/39 (15.4%) 7
    Hypokalemia 1/3 (33.3%) 1 1/3 (33.3%) 1 12/39 (30.8%) 13
    Hypomagnesemia 0/3 (0%) 0 2/3 (66.7%) 2 6/39 (15.4%) 7
    Hyperglycemia 0/3 (0%) 0 0/3 (0%) 0 4/39 (10.3%) 4
    Hypophosphatemia 0/3 (0%) 0 0/3 (0%) 0 5/39 (12.8%) 6
    Hypocalcemia 0/3 (0%) 0 1/3 (33.3%) 1 2/39 (5.1%) 3
    Musculoskeletal and connective tissue disorders
    Back Pain 2/3 (66.7%) 2 1/3 (33.3%) 1 6/39 (15.4%) 6
    Bone Pain 0/3 (0%) 0 3/3 (100%) 3 6/39 (15.4%) 7
    Myalgia 1/3 (33.3%) 1 2/3 (66.7%) 3 2/39 (5.1%) 2
    Pain in Extremity 0/3 (0%) 0 0/3 (0%) 0 5/39 (12.8%) 5
    Arthralgia 2/3 (66.7%) 2 0/3 (0%) 0 3/39 (7.7%) 5
    Nervous system disorders
    Headache 3/3 (100%) 5 1/3 (33.3%) 1 15/39 (38.5%) 18
    Dizziness 1/3 (33.3%) 1 1/3 (33.3%) 1 4/39 (10.3%) 5
    Peripheral Sensory Neuropathy 2/3 (66.7%) 3 1/3 (33.3%) 1 10/39 (25.6%) 12
    Psychiatric disorders
    Anxiety 1/3 (33.3%) 1 0/3 (0%) 0 5/39 (12.8%) 5
    Insomnia 0/3 (0%) 0 1/3 (33.3%) 1 4/39 (10.3%) 4
    Respiratory, thoracic and mediastinal disorders
    Cough 1/3 (33.3%) 1 1/3 (33.3%) 1 6/39 (15.4%) 6
    Dyspnea 0/3 (0%) 0 1/3 (33.3%) 3 2/39 (5.1%) 2
    Allergic Rhinitis 0/3 (0%) 0 0/3 (0%) 0 7/39 (17.9%) 7
    Skin and subcutaneous tissue disorders
    Alopecia 3/3 (100%) 3 1/3 (33.3%) 1 19/39 (48.7%) 19
    Rash maculo-papular 0/3 (0%) 0 0/3 (0%) 0 8/39 (20.5%) 8
    Pruritus 1/3 (33.3%) 1 1/3 (33.3%) 1 7/39 (17.9%) 8

    Limitations/Caveats

    [Not Specified]

    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 Dr. Ajay Gopal
    Organization University of Washington
    Phone 26-606-2037
    Email agopal@uw.edu
    Responsible Party:
    Ajay Gopal, Professor, Department of Medicine, Division of Oncology, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02227199
    Other Study ID Numbers:
    • 9111
    • NCI-2014-01782
    • 9111
    • P30CA015704
    • RG1714038
    First Posted:
    Aug 28, 2014
    Last Update Posted:
    Jun 30, 2022
    Last Verified:
    Jun 1, 2022