Clinical Trials /

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

NCT02227199

Description:

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.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 9111
  • SECONDARY ID: NCI-2014-01782
  • SECONDARY ID: 9111
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT02227199

Conditions

  • Recurrent Adult Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • TNFRSF8 Positive

Interventions

DrugSynonymsArms
Brentuximab VedotinADC 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-35Treatment (brentuximab, ifosfamide, carboplatin, etoposide)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (brentuximab, ifosfamide, carboplatin, etoposide)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Treatment (brentuximab, ifosfamide, carboplatin, etoposide)
IfosfamideAsta 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-4942Treatment (brentuximab, ifosfamide, carboplatin, etoposide)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (brentuximab, ifosfamide, carboplatin, etoposide)ExperimentalPatients 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
  • Carboplatin
  • Etoposide
  • Ifosfamide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:Described from the time of initiation of study therapy and from ASCT (for those who go on to receive this treatment).
Measure:Progression-free survival
Time Frame:Up to 5 years
Safety Issue:
Description: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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

September 16, 2019