Clinical Trial: A Phase 1 Study in Patients With Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1 Study to Estimate MMAE Metabolites in Human Plasma and Urine in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma or Relapsed or Refractory Systemic Anapl

Brief Summary: This is an open-label trial to estimate the concentrations of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma (HL) or relapsed/refractory systemic anaplastic large cell lymphoma (sALCL) participants treated with either brentuximab vedotin or brentuximab vedotin + rifampicin.

Detailed Summary:
Sponsor: Millennium Pharmaceuticals, Inc.

Current Primary Outcome:

  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, Predose [ Time Frame: Cycle 1: Predose ]
    Metabolites of MMAE includes C4, C5, C7, C8 and C13. The lower limit of Quantification (LLQ) for all the observations was 0.01 nanogram/milliliter (ng/mL).
  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, Predose [ Time Frame: Cycle 2: Predose ]
    Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, Predose [ Time Frame: Cycle 3: Predose ]
    Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 1, 0.5 Hour Postdose [ Time Frame: Cycle 1: 0.5 hour postdose ]
    Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 2, 0.5 Hour Postdose [ Time Frame: Cycle 2: 0.5 hour postdose ]
    Metabolites of MMAE includes C4, C5, C7, C8 and C13. The LLQ for all the observations was 0.01 ng/mL.
  • Plasma Concentration of Monomethylauristatin E (MMAE) and Its Metabolites at Cycle 3, 0.5 Hour Postdose [ Time Frame: Cycle 3: 0.5 hour postdose ]<

    Original Primary Outcome: Plasma and urine concentrations of MMAE and its major metabolites [ Time Frame: Various timepoints during Day 1 of Cycles 1 and 3 ]

    Current Secondary Outcome:

    • Serum Concentrations of Antibody-drug Conjugate (ADC) [ Time Frame: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose ]
      The LLQ for all the observations was 12.5 ng/mL.
    • Serum Concentration of Total Antibody (TAb) [ Time Frame: Cycle 1 and 3: Predose, 0.5, 4, 72, 336 hours post-dose; Cycle 2: Predose, 0.5 hours post-dose; Cycle 3: 480 hours post-dose ]
      The LLQ for all the observations was 12.5 ng/mL.
    • Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after last dose of study drug (30 days after Cycle 16) ]
      An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. AEs included both SAE and non-SAE.
    • Number of Participants With Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin [ Time Frame: Day 1 of Cycle 1 and 3 ]
      Participants with positive ATA at both Cycle 1 and 3, negative ATA at both Cycle 1 and 3, and transient positive (positive at one time point, but negative at the other) ATA for brentuximab vedotin were reported.
    • Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16) ]
      The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
    • Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline up to 30 days after last dose of study drug (30 Days after Cycle 16) ]
      Vital signs included body temperature, body weight, blood pressure and heart rate.


    Original Secondary Outcome:

    • Serum concentrations of ADC and TAb (free and ADC-bound) [ Time Frame: Various timepoints during Day 1 of Cycles 1 and 3 ]
    • The presence of ATA to brentuximab vedotin [ Time Frame: Day 1 of Cycle 1 and 3 ]
    • AEs, serious adverse events (SAEs), assessments of clinical laboratory values, and vital sign measurements [ Time Frame: From signing informed consent through 30 days after the last dose of study drug ]


    Information By: Millennium Pharmaceuticals, Inc.

    Dates:
    Date Received: September 23, 2013
    Date Started: November 2013
    Date Completion:
    Last Updated: March 30, 2016
    Last Verified: March 2016