A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas
I. To evaluate the safety of brentuximab vedotin and rituximab in patients with lymphoid
malignancies that are cluster of differentiation (CD) 30 positive (+) and/or Epstein-Barr
virus (EBV)+, and to determine the recommended phase 2 dose (RP2D) of the combination.
(Phase I) II. To evaluate the efficacy, as measured by response rates, of brentuximab
vedotin and rituximab in patients with lymphoid malignancies that are CD30+ and/or EBV+.
I. To further evaluate the frequency and severity of toxicity. (Phase II) II. To further
evaluate the clinical efficacy of the combination of brentuximab vedotin and rituximab, as
measured by progression free survival (PFS) and overall survival (OS) at one year after the
end of treatment. (Phase II) III. To determine the effects of the combination of brentuximab
vedotin and rituximab on markers of EBV activation and proliferation. (Phase II) IV. Further
evaluate efficacy as measured by time to cytotoxic chemotherapy. (Phase II) V. Further
evaluate efficacy as measured by observed rates of graft rejection. (Phase II)
I. To determine whether and to what extent CD30 expression predicts for response and
II. To determine whether and to what extent expression of EBV markers predicts for response
III. To determine whether changes in serum levels of EBV correlate with response and
subsequent loss of response to therapy.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase
INDUCTION: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes once
weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve
complete remission (CR) may receive additional optional consolidation therapy identical to
MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and
rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, and
then every 6 months for 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
For Phase I: Determine the Dose Limiting Toxicity (DLT) of brentuximab vedotin and rituximab in combination
The DLT of brentuximab vedotin and rituximab in combination will be assessed at baseline and each week during the first 21 days (1 cycle=21 days).
The 1st 21 days
Adam Petrich, MD
United States: Institutional Review Board
|Northwestern University||Chicago, Illinois 60611|
|University of Chicago||Chicago, Illinois 60637|
|University of Massachusetts Memorial Health Care||Worcester, Massachusetts 01605|