Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT - 2)

• ClinicalTrials.gov Identifier: NCT01239797
• Recruitment Status: Completed
• First Posted: November 11, 2010
• Results First Posted: January 5, 2017
• Last Update Posted: June 1, 2022
• Sponsor: Bristol-Myers Squibb
• Collaborator: AbbVie
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 8, 2010
• First Posted Date: November 11, 2010
• Results First Submitted Date: August 4, 2016
• Results First Posted Date: January 5, 2017
• Last Update Posted Date: June 1, 2022
• Actual Study Start Date: June 20, 2011
• Actual Primary Completion Date: September 2, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2022)

• Median Progression Free Survival (PFS) [ Time Frame: From randomization up to 326 events (up to approximately 38 months) ]
  Primary definition of Progression-free survival (PFS) defined as the time from randomization to the date of first documented tumor progression or death due to any cause. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. The primary analysis of PFS was based on the primary definition using the Independent Review Committee (IRC) tumor assessment using the European Group for Blood and Bone Marrow Transplant (EBMT) criteria. Tumor assessments were made every 4 weeks (±1 week) relative to the first dose of study medication.
• Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 38 months ]
  Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks.

• Original Primary Outcome Measures (submitted: November 10, 2010): Progression-free survival (PFS) - Time from randomization to date of first tumor progression or death due to any cause, provided death is not more than 10 weeks after the last tumor assessment [ Time Frame: Tumor assessments every 4 weeks (±1 week) relative to the first dose of study medication (median length of time for tumor assessments should be approximately 13 months) ]

Current Secondary Outcome Measures (submitted: May 5, 2022)

• Median Overall Survival (OS) [ Time Frame: Randomization to the date of death from any cause (up to approximately 9 years) ]
  Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has not died, their survival time will be censored at the date of last contact ("last known alive date"). A subject will be censored at the date of randomization if they were randomized but had no follow-up. (Based on Kaplan Meier estimates)
• Change From Baseline of Mean Score Pain Severity (BPI-SF) [ Time Frame: From baseline up to approximately 38 months ]
  The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.
• Change From Baseline of Mean Score Pain Interference (BPI-SF) [ Time Frame: From baseline up to approximately 38 months ]
  The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 ("No pain", "No interference") to 10 ("Pain as bad as you can imagine", "Highest imaginable interference") numeric rating scale.

Original Secondary Outcome Measures (submitted: November 10, 2010)

• Objective Response Rate - The percentage of patients who have a partial or complete response to study therapy [ Time Frame: All response endpoints assessed every 4 weeks (± 1 week) (median length of the endpoint assessment period is projected to be approximately 13 months) ]
• Overall Survival - The period of time from study entry until the date of death or last known date alive [ Time Frame: Survival will be assessed every 12 weeks in the Follow Up Phase of the trial (approximate length of the overall survival period is 6.75 years) ]

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

Descriptive Information

• Brief Title: Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma
• Official Title: Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma (MM)
• Brief Summary: The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphoma
• Multiple Myeloma

Intervention

• Drug: Lenalidomide
  Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug
  Other Name: Revlimid®
• Drug: Dexamethasone
  Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug
  Other Names:

  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
• Drug: Dexamethasone (Oral)

  On weeks without Elotuzumab dosing: Tablets, Oral, 40mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug.

  On weeks with Elotuzumab dosing: Tablets, Oral, 28 mg, Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Other Names:

  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
• Drug: Dexamethasone (IV)

  On weeks without Elotuzumab dosing: Not Applicable (N/A)

  On weeks with Elotuzumab dosing: Solution, Intravenous (IV), 8 mg, weekly, Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Other Names:

  • Decadron®
  • Dexamethasone Intensol®
  • Dexpak®
  • Taperpak®
• Biological: Elotuzumab (BMS-901608; HuLuc63)
  Solution, IV, 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

Study Arms

• Active Comparator: Lenalidomide + Dexamethasone
  Interventions:

  • Drug: Lenalidomide
  • Drug: Dexamethasone
• Experimental: Lenalidomide + Dexamethasone +Elotuzumab
  Interventions:

  • Drug: Lenalidomide
  • Drug: Dexamethasone (Oral)
  • Drug: Dexamethasone (IV)
  • Biological: Elotuzumab (BMS-901608; HuLuc63)

Publications *

• Dimopoulos MA, Lonial S, Betts KA, Chen C, Zichlin ML, Brun A, Signorovitch JE, Makenbaeva D, Mekan S, Sy O, Weisel K, Richardson PG. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018 Oct 15;124(20):4032-4043. doi: 10.1002/cncr.31680. Epub 2018 Sep 11.
• Passey C, Mora J, Dodge R, Gibiansky L, Sheng J, Roy A, Bello A, Gupta M. An Integrated Assessment of the Effects of Immunogenicity on the Pharmacokinetics, Safety, and Efficacy of Elotuzumab. AAPS J. 2017 Mar;19(2):557-567. doi: 10.1208/s12248-016-0033-9. Epub 2017 Jan 9.
• Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Rollig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015 Aug 13;373(7):621-31. doi: 10.1056/NEJMoa1505654. Epub 2015 Jun 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 5, 2022): 646
• Original Estimated Enrollment (submitted: November 10, 2010): 640
• Actual Study Completion Date: April 21, 2021
• Actual Primary Completion Date: September 2, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Documented progression from most recent line of therapy
• 1-3 prior lines of therapy
• Measurable disease
• Life expectancy ≥3 months

• Prior treatment with Lenalidomide permitted if:

  1. Best response achieved was ≥Partial Response (PR)
  2. Patient was not refractory
  3. Patient did not discontinue due to a Grade ≥3 related adverse event
  4. Subject did not receive more than 9 cycles of Lenalidomide and had at least 9 months between the last dose of Lenalidomide and progression

Exclusion Criteria:

• Subjects with non-secretory or oligo-secretory or serum free light-chain only myeloma
• Active plasma cell leukemia
• Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C

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, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Poland, Puerto Rico, Romania, Spain, Switzerland, Turkey, United Arab Emirates, United Kingdom, United States
• Removed Location Countries: Czech Republic, Russian Federation

Administrative Information

• NCT Number: NCT01239797
• Other Study ID Numbers: CA204-004; 2010-020347-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Study Director, Bristol-Myers Squibb
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: AbbVie

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: May 2022