A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT01421667
• Recruitment Status: Completed
• First Posted: August 23, 2011
• Results First Posted: October 13, 2016
• Last Update Posted: November 28, 2016
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: August 19, 2011
• First Posted Date: August 23, 2011
• Results First Submitted Date: June 21, 2016
• Results First Posted Date: October 13, 2016
• Last Update Posted Date: November 28, 2016
• Study Start Date: August 2011
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2016)

• Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy [ Time Frame: Up to approximately 3 years ]
  Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
• Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab [ Time Frame: Up to 3 years ]
  Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.

• Original Primary Outcome Measures (submitted: August 19, 2011): Objective response rate [ Time Frame: Through 1 month following last dose ]

Current Secondary Outcome Measures (submitted: October 14, 2016)

• Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab [ Time Frame: Up to approximately 3 years ]
  Percentage of participants treated with brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
• Complete Remission (CR) Rate by Investigator [ Time Frame: Up to approximately 3 years ]
  Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
• Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [ Time Frame: Up to approximately 3 years ]
  Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
• Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [ Time Frame: Up to approximately 3 years ]
  Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
• Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [ Time Frame: Up to approximately 3 years ]
  Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
• Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression [ Time Frame: Up to 3 years ]
  Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
• Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy [ Time Frame: Up to 3 years ]
  Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
• Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) [ Time Frame: 1 day ]
  End of infusion concentration of ADC following the first dose of brentuximab vedotin
• Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) [ Time Frame: 3 weeks ]
  Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
• Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) [ Time Frame: 3 weeks ]
  Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
• Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) [ Time Frame: 3 weeks ]
  Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
• Baseline Soluble CD30 Expression [ Time Frame: Baseline ]
  Serum concentration of soluble CD30 before first dose of brentuximab vedotin

Original Secondary Outcome Measures (submitted: August 19, 2011)

• Complete remission (CR) rate [ Time Frame: Through 1 month following last dose ]
• Incidence of adverse events [ Time Frame: Through 1 month following last dose ]
• Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose ]
• Correlation between CD30 expression and antitumor activity [ Time Frame: Through 1 month following last dose ]
• Duration of response [ Time Frame: Until disease progression or study closure ]
• Progression-free survival [ Time Frame: Until disease progression or study closure ]
• Area under the plasma concentration versus time curve (AUC) [ Time Frame: Cycle 1: pre-dose, end of infusion and 24, 48, 168, and 336 hours post-dose. Cycles 2 and later: pre-dose and end of infusion ]
• Peak plasma concentration (Cmax) [ Time Frame: Cycle 1: pre-dose, end of infusion and 24, 48, 168, and 336 hours post-dose. Cycles 2 and later: pre-dose and end of infusion ]
• Plasma concentration at end of infusion (Ceoi) [ Time Frame: Cycle 1: pre-dose, end of infusion and 24, 48, 168, and 336 hours post-dose. Cycles 2 and later: pre-dose and end of infusion ]
• Pharmacodynamic (PD) biomarkers [ Time Frame: Pre-dose at each cycle ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma
• Official Title: A Phase 2 Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL)
• Brief Summary: This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell

Intervention

• Drug: brentuximab vedotin
  1.8 mg/kg every 3 weeks by IV infusion
  Other Name: Adcetris; SGN-35
• Drug: rituximab
  375 mg/m2 every 3 weeks by IV infusion

Study Arms

• Experimental: Brentuximab vedotin+rituximab
  Interventions:

  • Drug: brentuximab vedotin
  • Drug: rituximab
• Experimental: Brentuximab vedotin
  Intervention: Drug: brentuximab vedotin

Publications *

• Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O'Connor OA, Siddiqi T, Kennedy DA, Oki Y. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. doi: 10.1182/blood-2013-12-542142. Epub 2014 Mar 20.
• Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. doi: 10.1182/blood-2014-09-598763. Epub 2015 Jan 8.
• Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. doi: 10.1080/10428194.2016.1256481. Epub 2016 Nov 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 13, 2014): 176
• Original Estimated Enrollment (submitted: August 19, 2011): 55
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically-confirmed NHL (DLBCL only for Parts B and C)
• Relapsed or refractory disease following at least 1 prior systemic therapy
• Measurable disease of at least 1.5 cm as documented by CT
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Exclusion Criteria:

• History of another primary invasive malignancy that has not been in remission for at least 3 years
• Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides
• B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy
• Known cerebral/meningeal disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01421667
• Other Study ID Numbers: SGN35-012
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Corinna Palanca-Wessels, MD, PhD; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: June 2015