Clinical Trials /

Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients With Hodgkin Lymphoma

NCT01393717

Description:

This phase II trial studies how well brentuximab vedotin before autologous (taken from an individual's own cells) stem cell transplant works in treating patients with Hodgkin lymphoma. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Brentuximab Vedotin</span> Before Autologous <span class="go-doc-concept go-doc-intervention">Stem Cell Transplant</span> in Treating Patients With <span class="go-doc-concept go-doc-disease">Hodgkin Lymphoma</span>

Title

  • Brief Title: Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients With Hodgkin Lymphoma
  • Official Title: A Phase II Study of Brentuximab Vedotin as Salvage Therapy for Hodgkin Lymphoma Prior to Autologous Hematopoietic Stem Cell Transplantation
  • Clinical Trial IDs

    NCT ID: NCT01393717

    ORG ID: 11051

    NCI ID: NCI-2011-01135

    Trial Conditions

    Recurrent Hodgkin Lymphoma

    Refractory Hodgkin Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    brentuximab vedotin anti-CD30 ADC SGN-35, anti-CD30 antibody-drug conjugate SGN-35, antibody-drug conjugate SGN-35, SGN-35, Adcetris Treatment (brentuximab vedotin)

    Trial Purpose

    This phase II trial studies how well brentuximab vedotin before autologous (taken from an
    individual's own cells) stem cell transplant works in treating patients with Hodgkin
    lymphoma. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer
    growth in different ways by targeting certain cells.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. The primary objective of this study is to determine the activity of salvage brentuximab
    vedotin in Hodgkin lymphoma prior to autologous hematopoietic stem cell transplantation, as
    measured by overall response rate (ORR).

    SECONDARY OBJECTIVES:

    I. To describe the safety, toxicity, and tolerability of brentuximab vedotin as a salvage
    regimen.

    II. To summarize the stem cell mobilization results of patients receiving brentuximab
    vedotin as salvage therapy (e.g., total cluster of differentiation (CD)34+ cell yield,
    number of apheresis days, proportion of patients who achieve >= 3 x 10^6 CD34+ cells/kg).

    III. To evaluate potential changes in Hodgkin lymphoma biological markers of patients
    treated with brentuximab vedotin as first line salvage therapy.

    IV. To examine and characterize the outcomes of patients who receive brentuximab vedotin as
    first line salvage followed by autologous hematopoietic stem cell transplantation (AHCT)
    (e.g., toxicity, 2-year progression free survival [PFS], overall survival [OS],
    relapse-progression incidence and non-relapse mortality rate [NRM])

    OUTLINE:

    Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment
    repeats every 21 days for up to 4 courses.

    Patients in the new cohort receive regular study dose of brentuximab vedotin for courses 1
    and 2. Patients not achieving complete remission (CR) after 2 courses receive higher-dose
    brentuximab vedotin IV over 60 minutes on day 1 for 2 additional courses.

    After completion of study treatment, patients are followed up at 21 days.

    Trial Arms

    Name Type Description Interventions
    Treatment (brentuximab vedotin) Experimental Patients receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses. Patients in the new cohort receive regular study dose of brentuximab vedotin for courses 1 and 2. Patients not achieving CR after 2 courses receive higher-dose brentuximab vedotin IV over 60 minutes on day 1 for 2 additional courses. brentuximab vedotin

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have histologically documented or cytologically confirmed Hodgkin
    lymphoma with CD 30 expression

    - Patients must have absolute neutrophil count (ANC) >= 1000/uL; neupogen (filgrastim)
    can be given prior to start of SGN-35 (brentuximab vedotin) and during SGN-35
    treatment to achieve target ANC >= 1000/uL

    - Patients must have platelets (Plts) >= 50,000/uL; platelet transfusion can be given
    prior to the start of SGN-35 and during SGN-35 treatment to achieve a target plt >=
    50,000/uL

    - Patients must have measurable disease > 1.5 cm evidenced by computed tomography (CT)
    scan of the neck/chest/abdomen(abd)/pelvis or CT/positron emission tomography (PET)
    scans

    - Patient must be either primary refractory to one frontline induction therapy or
    relapsed after one frontline induction therapy; patients who do not achieve complete
    remission after induction therapy are also eligible

    - Patients cannot have had a second line salvage treatment (chemotherapy, biologic
    agents, investigational drugs, or radiation) or have had an autologous or allogeneic
    hematopoietic stem cell transplantation; patients can have had mixed frontline
    therapy such as 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine and
    dacarbazine) followed by 2-4 cycles of bleomycin, etoposide, doxorubicin,
    cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as long as the
    induction chemotherapy is not more than 8 cycles in total length

    - Radiation use as part of induction regimen or consolidation (within 90 days after
    completion of induction chemotherapy) is allowed

    - Voluntary written informed consent before performance of any study-related procedure
    not part of normal medical care, with the understanding that consent may be withdrawn
    by the subject at any time without prejudice to future medical care

    - Female subject is either post-menopausal or surgically sterilized or willing to use
    an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
    device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
    duration of the study

    - Male subject agrees to use an acceptable method of contraception for the duration of
    the study

    - Life expectancy of greater than 3 months

    - Karnofsky performance status of > 60%

    - ANC >= 1000/uL

    - Plts >= 50,000/uL

    - Total bilirubin within 1.5 x of the upper limit of normal (ULN) institutional limits,
    patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are
    eligible

    - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 X institutional
    ULN (unless demonstrated Hodgkin lymphoma involvement of the liver)

    - Calculated creatinine clearance >30 ml/min (unless demonstrated Hodgkin lymphoma
    involvement of the kidney)

    ELIGIBILITY FOR 2.4 MG/KG DOSING IN THE NEW COHORT:

    - In addition to the inclusion/exclusion criteria outlined, to be eligible for treatment
    with the higher 2.4 mg/kg dose of brentuximab vedotin in the new cohort of 20 additional
    patients, best response after 2 cycles of brentuximab vedotin administered at the 1.8
    mg/kg dose, must be partial remission (PR) or stable disease (SD) as determined by
    radiographic imaging

    Exclusion Criteria:

    - Patient has > 1.5 x ULN total bilirubin, unless history of Gilbert's syndrome

    - Myocardial infarction within 6 months prior to enrollment or has New York Heart
    Association (NYHA) class III or IV heart failure, uncontrolled angina, severe
    uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
    ischemia or active conduction system abnormalities; prior to study entry, any
    electrocardiogram (ECG) abnormality at screening has to be documented by the
    investigator as not medically relevant

    - Patient has hypersensitivity to brentuximab vedotin

    - Female subject is pregnant or breast-feeding; confirmation that the subject is not
    pregnant must be established by a negative serum beta-human chorionic gonadotropin
    (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not
    required for post-menopausal or surgically sterilized women

    - Patient has received other investigational drugs within 14 days before treatment of
    treatment with brentuximab vedotin

    - Serious medical or psychiatric illness likely to interfere with participation in this
    clinical study

    - Diagnosed or treated for another malignancy within 3 years of enrollment, with the
    exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
    the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

    - Patients with other active malignancies (no evidence of other cancer or life
    expectancy greater than 5 years) are ineligible for this study

    - Patients with active central nervous system (CNS) disease or history of brain
    metastases (mets) are excluded from study

    - Patients may be on steroids prior to initiation of treatment as long as by cycle 1
    day 1 steroids use was tapered down less than or equal to 20 mg of prednisone.

    Minimum Eligible Age: 11 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall response rate of salvage brentuximab vedotin treatment for Hodgkin lymphoma before autologous hematopoietic stem cell transplantation

    CR rate (new cohort)

    Secondary Outcome Measures

    Safety, toxicity, and tolerability of brentuximab vedotin as a salvage regimen as determined by incidence of adverse events and lab abnormalities

    Stem cell mobilization results of patients receiving brentuximab vedotin as salvage therapy for patients that are proceeding to autologous hematopoietic stem cell transplantation

    Potential changes in Hodgkin lymphoma biological markers of patients treated with brentuximab vedotin

    PFS defined as the time from first treatment day (post AHCT) until objective or symptomatic relapse or death as a result of lymphoma or acute toxicity of treatment

    OS defined as the time from first treatment day (post AHCT) until death

    Trial Keywords