CD30-positive Lymphoma Clinical Trial
Official title:
A Phase I Study of the Combination of Alsertib (MLN8237) and Brentuximab Vedotin in Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies
This is an open label phase I trial designed to evaluate the maximum tolerated dose, dose-limiting toxicities, pharmacokinetics, and activity of the combination of alsertib (MLN8237) and brentuximab vedotin in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies. Cohorts of 3-6 patients will receive escalating or de-escalating doses of MLN8237 based on a 3 + 3 design.
This is an investigator-initiated, open label phase I trial designed to evaluate the maximum
tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and activity of
brentuximab vedotin in combination with MLN8237 in patients with relapsed/refractory
CD30-positive lymphomas and solid malignancies.
Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered on Day 1 every three
weeks as a 30-minute outpatient intravenous infusion. MLN8237 will be orally administered in
two divided doses from Days 1-7. The starting dose (level 0) of MLN8237 will be 60 mg daily
given in two divided doses (30 mg qAM, 30 mg qPM).The dose of MLN8237 will be escalated in
20-mg increments up to 100 mg daily and de-escalated in 20-mg decrements to 40 mg daily. The
fixed dose of brentuximab vedotin on Day 1 and daily dose of MLN8237 on Day 1-7 will
constitute one treatment cycle. If no DLTs are observed in the last study cohort, the cohort
will be expanded to include a total of 12 patients. If a de-escalation dose is required
because 2 or more patients experience DLTs, the next lower cohort will be studied. If 2 or
more patients do not experience DLTs, this dose will be declared the MTD. This cohort will be
expanded to include 12 patients in order to study the biological endpoints and clinical
benefit of the combination. If at any point during the expansion cohort phase of the trial
33% or more of the patients treated at the MTD/maximum administered dose experience a DLT,
accrual of additional patients at this does level will cease and the next lowest dose may be
explored.
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