Brentuximab Vedotin Before Autologous Stem Cell Transplant in Treating Patients With Hodgkin Lymphoma
Condition: Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: brentuximab vedotin
Intervention description: Given IV
Intervention MeSH terms: Brentuximab Vedotin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoconjugates
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 11 Years
Healthy volunteers: No

Summary:

      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.
    

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.