Clinical Trial: Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas

Brief Summary: The purpose of this study is to evaluate how safe and effective the combination of two different drugs (brentuximab vedotin and rituximab) is in patients with certain types of lymphoma. This study is for patients who have a type of lymphoma that expresses a tumor marker called CD30 and/or a type that is associated with the Epstein-Barr virus (EBV-related lymphoma) and who have not yet received any treatment for their cancer, except for dose-reduction or discontinuation (stoppage) of medications used to prevent rejection of transplanted organs (for those patients who have undergone transplantation). This study is investigating the combination of brentuximab vedotin and rituximab as a first treatment for lymphoma patients

Detailed Summary:

PRIMARY OBJECTIVES:

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+. (Phase II)

SECONDARY OBJECTIVES:

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)

TERTIARY OBJECTIVES:

I. To determine whether and to what extent CD30 expression predicts for response and outcome.

II. To determine whether and to what extent expression of EBV markers predicts for response and outcome.

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 phas
Sponsor: Northwestern University

Current Primary Outcome:

  • For Phase I: Determine the Dose Limiting Toxicity (DLT) of brentuximab vedotin and rituximab in combination [ Time Frame: The 1st 21 days ]
    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).
  • Phase I: Determine the Maximum Tolerated Dose (MTD) of brentuximab vedotin and rituximab in combination [ Time Frame: The 1st 21 days ]
    The safety of brentuximab vedotin and rituximab in combination will be assessed at baseline and each week during the first 21 days (1 cycle=21 days) which will assist in providing the MTD, also known as the Recommended Phase II Dose, which will be the dose given in Phase II of the trial.
  • For Phase II: Efficacy of study treatment will be measured by anti-tumor activity as detected from imaging scans [ Time Frame: Prior to beginning treatment in week 5 ]
    The efficacy, or anti-tumor activity, of brentuximab vedotin and rituximab will be measured at baseline and before receiving treatment in week 5. This will be evaluated by assessing PET or CT imaging scans.
  • For Phase II: Efficacy of study treatment will be measured by anti-tumor activity as detected from imaging scans [ Time Frame: Prior to beginning treatment in week 11 ]
    The efficacy, or anti-tumor activity, of brentuximab vedotin and rituximab will be measured before receiving treatment in week 11. This will be evaluated by assessing PET or CT imaging scans.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Phase II: Further evaluate toxicity of treatment by evaluating adverse events [ Time Frame: Prior to dosing at week 5 or until disease progression (maximum 1 year) ]
    Toxicity, both frequency and severity, will continue to be measured by monitoring the occurence of adverse events. Assessments of toxicity will occur prior to treatment for week 5.
  • Phase II: Further evaluate toxicity of treatment by evaluating adverse events [ Time Frame: Prior to dosing at week 11 or until disease progression (maximum 1 year) ]
    Toxicity, both frequency and severity, will continue to be measured by monitoring the occurence of adverse events. Assessments of toxicity will occur prior to treatment for week 11.
  • Phase II: Further evaluate efficacy of treatment by measuring Progression Free Survival (PFS) [ Time Frame: Time elapsed from start of treatment to date of disease progression (maximum 3 years) ]
    Study treatment efficacy will be evaluated using PET or CT scan images to determine Progression Free Survival which is measured from treatment initiation until tumor progression
  • Phase II: Further evaluate efficacy of treatment by measuring Overall Survival (OS) [ Time Frame: Time elapsed from start of treatment to date of disease progression (maximum 3 years) ]
    Efficacy of treatment will be evaluated using PET or CT scan images to determine Overall Survival which is measured as time from treatment initiation until disease progression, patients will be followed up to 3 years.
  • Determining the effects of the combination of brentuximab vedotin and rituximab on biomarkers of Epstein-Barr Virus [ Time Frame: At baseline and once per cycle (1 cycle=3 weeks) for the duration of treatment up to 1 year ]
    The effect of study treatment on biomarkers of the Epstein-Barr Virus will be evaluated from blood collected at baseline and once per treatment cycle (every 3 weeks).
  • Continued efficacy of treatment evaluation as measured by time between treatment initiation and time of first cytotoxic chemotherapy [ Time Frame: Time from start of study treatment to time of first dose of cytotoxic chemotherapy (maximum of 1 year) ]
    Efficacy of study treatment will also be determined by evaluating the amount of time from start of study treatment to time of first dose of cytotoxic chemotherapy (administered to treat lymphoma).
  • Rates of graft rejection as another measurement of efficacy [ Time Frame: Time from 1st dose until end of treatment (maximum 1 year) ]
    Graft rejection during study treatment will be measured to evaluate therapy efficacy.


Original Secondary Outcome: Same as current

Information By: Northwestern University

Dates:
Date Received: February 27, 2013
Date Started: March 2013
Date Completion:
Last Updated: April 28, 2015
Last Verified: April 2015