Clinical trial NCT02076009: A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Official title: Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Daratumumab
Lenalidomide
Dexamethasone
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-03-03
Enrollment: 569
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma.

Detailed description: This is a randomized (participants will be assigned by chance to study treatments), open-label (all participants and study personnel will know the identity of the study treatments), active-controlled (none of the study treatments are placebo), parallel-group (both treatment arms will run at the same time), multicenter study. In this study, daratumumab, lenalidomide, and low-dose dexamethasone (DRd) will be compared with lenalidomide and low dose dexamethasone (Rd) in participants with relapsed or refractory multiple myeloma. Participants will be randomized in a 1:1 ratio to receive either DRd or Rd. The study will include a Screening Phase, a Treatment Phase (involving treatment cycles of approximately 28 days in length), and a Follow-up Phase. The Treatment Phase will extend from the administration of the first dose of study medication until disease progression or unacceptable toxicity. Participants will also discontinue study treatment if: they become pregnant; have their dose held for more than 28 days (or if 3 consecutive planned doses of daratumumab are missed for reasons other than toxicity); or for safety reasons (for example, adverse event). The Follow-up Phase will begin at the end of treatment and will continue until death, loss to follow-up, consent withdrawal for study participation, or the final overall survival (OS) analysis, whichever occurs first. Eligible participants from Rd group who have had sponsor confirmed disease progression will be offered the option for treatment with daratumumab monotherapy (of 28 days cycle). The primary endpoint will be progression-free survival (PFS). Analysis of the primary endpoint was performed at a pre-specified point determined by PFS events with a clinical cutoff of March 7, 2016 when 169 events of death or progression had occurred. The end of study is anticipated at approximately 6 years after the last participant is randomized. Blood and urine samples will be obtained at time points during the study, together with bone marrow aspirates/biopsies and skeletal surveys. Participant safety will be assessed throughout the study.

Eligibility criteria: Inclusion Criteria:

* Must have documented multiple myeloma and measurable disease
* Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
* Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
* Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
* If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a "wash-out period" defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy

Exclusion Criteria:

* Has received any of the following therapies: daratumumab or other anti-CD38 therapies
* Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment
* Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
* Has received autologous stem cell transplantation within 12 weeks before the date of randomization, or previously received an allogenic stem cell transplant (regardless of timing), or planning to undergo a stem cell transplant prior to progression of disease
* History of malignancy (other than multiple myeloma) within 5 years before the first dose of daratumumab monotherapy (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization to either disease progression or death whichever occurs first (up to 21 months)
Secondary outcomes:
measure: Time to Disease Progression (TTP)
timeFrame: From randomization to disease progression (up to 21 months)
measure: Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
timeFrame: From randomization to disease progression (up to 21 months)
measure: Percentage of Participants With Negative Minimal Residual Disease (MRD)
timeFrame: From randomization to the date of first documented evidence of PD (up to 87.5 months)
measure: Overall Response Rate
timeFrame: From randomization to disease progression (up to 21 months)
measure: Overall Survival (OS)
timeFrame: From randomization to date of death due to any cause (up to 87.5 months)
measure: Time to Response
timeFrame: From randomization up to first documented CR or PR (up to 21 months)
measure: Duration of Response (DOR)
timeFrame: From randomization to the date of first documented evidence of PD (up to 21 months)
measure: Time to Subsequent Anticancer Treatment
timeFrame: From randomization to date of start of subsequent anticancer treatment or death due to PD, whichever occured first (up to 87.5 months)
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Gainesville
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Bethesda
country: United States
state: Maryland
city: Columbia
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: New Brunswick
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Eugene
country: United States
state: Oregon
city: Spartanburg
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Camperdown
country: Australia
city: Geelong
country: Australia
city: Heidelberg
country: Australia
city: Malvern
country: Australia
city: South Brisbane
country: Australia
city: Southport
country: Australia
city: Anderlecht
country: Belgium
city: Antwerpen
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Surrey
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Copenhagen
country: Denmark
city: Odense
country: Denmark
city: Vejle
country: Denmark
city: Argenteuil
country: France
city: Caen
country: France
city: Lille
country: France
city: Limoges
country: France
city: Nantes Cedex 1
country: France
city: Paris
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Toulouse Cedex 9
country: France
city: Tours Cedex 9
country: France
city: Vandoeuvre les Nancy
country: France
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Hamburg
country: Germany
city: Hamm
country: Germany
city: Heidelberg
country: Germany
city: Jena
country: Germany
city: Karlsruhe
country: Germany
city: Koblenz
country: Germany
city: Köln
country: Germany
city: Saarbrücken
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Athens Attica
country: Greece
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Nahariya
country: Israel
city: Netanya
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Hitachi
country: Japan
city: Kanazawa
country: Japan
city: Kobe
country: Japan
city: Kurume
country: Japan
city: Matsuyama
country: Japan
city: Nagoya
country: Japan
city: Narita
country: Japan
city: Ohgaki
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Sendai-City
country: Japan
city: Shibukawa
country: Japan
city: Shibuya
country: Japan
city: Tachikawa
country: Japan
city: Tokyo
country: Japan
city: Gyeonggi-do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Zwolle
country: Netherlands
city: Brzozow
country: Poland
city: Chorzow
country: Poland
city: Gdansk
country: Poland
city: Legnica
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Slupsk
country: Poland
city: Wroclawa
country: Poland
city: Dzerzhinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Samara
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: La Laguna (Santa Cruz De Tenerife)
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Falun
country: Sweden
city: Göteborg
country: Sweden
city: Helsingborg
country: Sweden
city: Huddinge
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Changhua
country: Taiwan
city: Taichung City
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Birmingham
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
city: Southampton
country: United Kingdom
city: Surrey
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Cavo M, San-Miguel J, Usmani SZ, Weisel K, Dimopoulos MA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria V, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar S, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi N. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2022 Feb 10;139(6):835-844. doi: 10.1182/blood.2021011101.
citation: Plesner T, Dimopoulos MA, Oriol A, San-Miguel J, Bahlis NJ, Rabin N, Suzuki K, Yoon SS, Ben-Yehuda D, Cook G, Goldschmidt H, Grosicki S, Qin X, Fastenau J, Garvin W, Carson R, Renaud T, Gries KS. Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial. Br J Haematol. 2021 Jul;194(1):132-139. doi: 10.1111/bjh.17435. Epub 2021 Apr 6.
citation: Avet-Loiseau H, San-Miguel J, Casneuf T, Iida S, Lonial S, Usmani SZ, Spencer A, Moreau P, Plesner T, Weisel K, Ukropec J, Chiu C, Trivedi S, Amin H, Krevvata M, Ramaswami P, Qin X, Qi M, Sun S, Qi M, Kobos R, Bahlis NJ. Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR. J Clin Oncol. 2021 Apr 1;39(10):1139-1149. doi: 10.1200/JCO.20.01814. Epub 2021 Jan 29.
citation: Mateos MV, Spencer A, Nooka AK, Pour L, Weisel K, Cavo M, Laubach JP, Cook G, Iida S, Benboubker L, Usmani SZ, Yoon SS, Bahlis NJ, Chiu C, Ukropec J, Schecter JM, Qin X, O'Rourke L, Dimopoulos MA. Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica. 2020 Jan 31;105(2):468-477. doi: 10.3324/haematol.2019.217448. Print 2020.
citation: Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.