This is a phase 1/2 multicenter study to assess the safety and effectiveness of brentuximab vedotin and bendamustine, when given together, in patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma (ALCL) that has either returned or did not respond to initial treatment(s). Patients will be accrued at Columbia University Medical Center (CUMC) and at two subsites in Canada.
Brentuximab vedotin will be administered as an outpatient IV infusion on day 1 of each 21-day cycle. Bendamustine will be given as an outpatient infusion on days 1 and 2 of a 21-day cycle. Patients may receive prophylactic pegfilgrastim on day 3 of each cycle, or filgrastim for 5 to 10 days, per investigator's discretion. Patients can receive a maximum of 6 cycles of therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Dose escalation in phase I of the study from 1.2-1.8 mg/kg, IV infusions over 30 minutes on day 1 of each 21-day cycle.
Dose escalation in phase I of the study from 60-100 mg/m2, IV infusion on days 1 and 2 of each 21-day cycle.
(Non-experimental) Standard procedure prophylactic pegfilgrastim on day 3 of any subsequent cycle after cycle 1, or filgrastim for 5 to 10 days, per investigator's discretion.
Center for Lymphoid Malignancies at CUMC
New York, New York, United States
British Columbia Cancer Agency
Vancouver, British Columbia, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
Maximum Tolerated Dose (MTD) of Brentuximab Vedotin in Combination of Brentuximab Vedotin and Bendamustine (Phase 1)
This is to measure the highest dose that does not cause unacceptable side effects with the combination of brentuximab vedotin and bendamustine.
Time frame: 21 days
Maximum Tolerated Dose (MTD) of Bendamustine in Combination of Brentuximab Vedotin and Bendamustine (Phase 1)
This is to measure the highest dose that does not cause unacceptable side effects with the combination of brentuximab vedotin and bendamustine.
Time frame: 21 days
Number of Participants With Dose Limiting Toxicities (DLT) of Brentuximab Vedotin and Bendamustine in Phase 1
DLT is defined as any missed dose within cycle 1 or toxicity that was possibly related to the study drug occurring up to 7 days after completion of cycle 1 that resulted in a delay of initiation of cycle 2; grade 4 neutropenia that did not resolve to grade 2 or lower within 7 days; grade 4 thrombocytopenia lasting more than 7 days; grade 3 febrile neutropenia (absolute neutrophil count of \<1000 cells per μL with a single temperature of \>38·3°C or a sustained temperature of ≥38°C for \>1 h); and any grade 3 or worse non-haematological toxicity, with the specific exception of nausea, vomiting, diarrhoea, or dehydration lasting for more than 48 h in the setting of inadequate compliance with supportive care measures or grade 3 hypercholesterolaemia, hypertriglyceridaemia, constipation, or fatigue.
Time frame: 21 days
Overall Response Rate for the Combination of Brentuximab Vedotin and Bendamustine
The number of subjects whose cancer shrinks or disappears after study treatment
Time frame: Up to 3 years
Duration of Response (DoR) in Phase 1
Duration of response is defined as the time from documentation of a response to treatment to the first documentation of tumor progression, or death from any cause, whichever occurred first.
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Time frame: Up to 50 months
Progression Free Survival (PFS) in Phase 1
The length of time during and after the study treatment that a subject lives with the disease but it does not get worse.
Time frame: Up to 50 months
Overall Survival (OS) in Phase 1
The length of time from either the date of diagnosis or the start of study treatment that subjects diagnosed with the disease are still alive.
Time frame: Up to 50 months