ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas (ECHELON-2)

• ClinicalTrials.gov Identifier: NCT01777152
• Recruitment Status: Completed
• First Posted: January 28, 2013
• Results First Posted: July 30, 2019
• Last Update Posted: November 30, 2021
• Sponsor: Seagen Inc.
• Collaborator: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: January 23, 2013
• First Posted Date: January 28, 2013
• Results First Submitted Date: July 10, 2019
• Results First Posted Date: July 30, 2019
• Last Update Posted Date: November 30, 2021
• Actual Study Start Date: January 31, 2013
• Actual Primary Completion Date: August 15, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2021)

Progression-free Survival Per Independent Review Facility (IRF) [ Time Frame: Up to 60 months ]

The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first.

• Original Primary Outcome Measures (submitted: January 25, 2013): Progression-free survival per independent review facility (IRF) [ Time Frame: Until disease progression, subsequent anticancer chemotherapy, death, or study closure, up to 5 years post-treatment ]

Current Secondary Outcome Measures (submitted: November 1, 2021)

• Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL) [ Time Frame: Up to 60 months ]
  The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first.
• Complete Remission (CR) Rate Per IRF at End of Treatment (EOT) [ Time Frame: Up to 8.34 months ]
  The count of participants with CR per IRF following the completion of study treatment (at end of treatment or at the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma.
• Overall Survival (OS) [ Time Frame: Up to 90 months ]
  The time from randomization to death due to any cause.
• Objective Response Rate (ORR) Per IRF at End of Treatment [ Time Frame: Up to 8.34 months ]
  The count of participants with CR or partial response (PR) per IRF following the completion of study treatment (at end of treatment or the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma.
• Incidence of Adverse Events (AEs) [ Time Frame: Up to 8.28 months ]
  Any untoward medical occurrence in a clinical investigational participant administered a medicinal product which does not necessarily have a causal relationship with this treatment.
• Incidence of Laboratory Abnormalities [ Time Frame: Up to 8.28 months ]
  Number of participants who experienced a Grade 3 or higher laboratory toxicity.

Original Secondary Outcome Measures (submitted: January 25, 2013)

• Progression-free survival per IRF in patients with systemic anaplastic large cell lymphoma (sALCL) [ Time Frame: Until disease progression, subsequent anticancer chemotherapy, death, or study closure, up to 5 years post-treatment ]
• Complete remission rate per IRF at end of treatment [ Time Frame: Through 1 month following last dose ]
• Overall survival [ Time Frame: Until death or study closure, up to 7 years post-treatment ]
• Type, incidence, severity, seriousness, and relatedness of adverse events [ Time Frame: Through 1 month following last dose ]
• Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose ]

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

Descriptive Information

• Brief Title: ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas
• Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients With CD30-positive Mature T-cell Lymphomas
• Brief Summary: This is a double-blind, randomized, multicenter, phase 3 clinical trial to compare the efficacy and safety of brentuximab vedotin in combination with CHP with the standard-of-care CHOP in patients with CD30-positive mature T-cell lymphomas.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Anaplastic Large-Cell Lymphoma
• Non-Hodgkin Lymphoma
• T-Cell Lymphoma

Intervention

• Drug: brentuximab vedotin
  1.8 mg/kg every 3 weeks by IV infusion for 6-8 cycles
  Other Name: Adcetris; SGN-35
• Drug: doxorubicin
  50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles
• Drug: prednisone
  100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles
• Drug: vincristine
  1.4 mg/m2 (maximum 2 mg) every 3 weeks by IV infusion for 6-8 cycles
• Drug: cyclophosphamide
  750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles

Study Arms

• Active Comparator: CHOP
  cyclophosphamide, doxorubicin, vincristine, and prednisone
  Interventions:

  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: vincristine
  • Drug: cyclophosphamide
• Experimental: A+CHP
  brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone
  Interventions:

  • Drug: brentuximab vedotin
  • Drug: doxorubicin
  • Drug: prednisone
  • Drug: cyclophosphamide

Publications *

• Savage KJ, Horwitz SM, Advani R, Christensen JH, Domingo-Domenech E, Rossi G, Morschhauser F, Alpdogan O, Suh C, Tobinai K, Shustov A, Trneny M, Yuen S, Zinzani PL, Trumper L, Ilidge T, O'Connor OA, Pro B, Miao H, Bunn V, Fenton K, Fanale M, Puhlmann M, Iyer S. Role of stem cell transplant in CD30+ PTCL following frontline brentuximab vedotin plus CHP or CHOP in ECHELON-2. Blood Adv. 2022 Oct 11;6(19):5550-5555. doi: 10.1182/bloodadvances.2020003971.
• Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illes A, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Huttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trumper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2. Epub 2018 Dec 4. Erratum In: Lancet. 2019 Jan 19;393(10168):228.
• Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, Chen RW, Davies A, Illidge T, Huebner D, Kennedy DA, Shustov AR. Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. J Clin Oncol. 2014 Oct 1;32(28):3137-43. doi: 10.1200/JCO.2013.54.2456. Epub 2014 Aug 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 7, 2016): 452
• Original Estimated Enrollment (submitted: January 25, 2013): 300
• Actual Study Completion Date: October 2, 2020
• Actual Primary Completion Date: August 15, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with newly diagnosed, CD30-positive mature T-cell lymphomas
• Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm 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 primary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas or mycosis fungoides
• History of progressive multifocal leukoencephalopathy (PML)
• Cerebral/meningeal disease related to the underlying malignancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Poland, Romania, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01777152
• Other Study ID Numbers: SGN35-014; 2012-002751-42 ( EudraCT Number )
• 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: Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Thomas Manley, MD; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: November 2021