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.
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.
