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

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ClinicalTrials.gov Identifier: NCT02227199
Recruitment Status : Recruiting
First Posted : August 28, 2014
Last Update Posted : November 12, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE August 25, 2014
First Posted Date  ICMJE August 28, 2014
Last Update Posted Date November 12, 2018
Actual Study Start Date  ICMJE October 10, 2014
Estimated Primary Completion Date September 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2018)
  • Maximum tolerated dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide chemotherapy, defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity [ Time Frame: Up to 28 days after the last dose of study drug ]
    Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
  • Percentage of patients that achieve a complete remission following study treatment [ Time Frame: 3 weeks following the second course of chemotherapy ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2014)
  • Maximum tolerated dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide chemotherapy, defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity [ Time Frame: Up to 28 days after the last dose of study drug ]
  • Percentage of patients that achieve a complete remission following study treatment [ Time Frame: 3 weeks following the second course of chemotherapy ]
Change History Complete list of historical versions of study NCT02227199 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2018)
  • Overall survival [ Time Frame: Up to 5 years ]
    Described from the time of initiation of study therapy and from ASCT (for those who go on to receive this treatment).
  • Progression-free survival [ Time Frame: Up to 5 years ]
    Described from the time of initiation of study therapy and from autologous stem cell transplantation (ASCT) (for those who go on to receive this treatment).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2014)
  • Progression-free survival [ Time Frame: Up to 5 years ]
    Described from the time of initiation of study therapy and from ASCT (for those who go on to receive this treatment).
  • Overall survival [ Time Frame: Up to 5 years ]
    Described from the time of initiation of study therapy and from ASCT (for those who go on to receive this treatment).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
Official Title  ICMJE 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)
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. Drugs used in chemotherapy, 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.
Detailed Description

PRIMARY OBJECTIVES:

I. 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.

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

SECONDARY OBJECTIVES:

I. To determine the safety and toxicity of the above regimen.

II. 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).

III. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Adult Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • TNFRSF8 Positive
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Treatment (brentuximab, ifosfamide, carboplatin, etoposide)
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.
Interventions:
  • Drug: Brentuximab Vedotin
  • Drug: Carboplatin
  • Drug: Etoposide
  • Drug: Ifosfamide
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2017)
42
Original Estimated Enrollment  ICMJE
 (submitted: August 25, 2014)
30
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date September 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02227199
Other Study ID Numbers  ICMJE 9111
NCI-2014-01782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9111 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP