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Multiple MyelomaPhase 3OCEANNCT03151811

A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide

A Phase 3 study testing Melflufen, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Oncopeptides AB at 105 sites in 21 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Melflufen, Pomalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
495 participants
Where
105 sitesin 21 countries
Study dates
12 Jun 2017to 3 Feb 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age 18 years or older
  • A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening
  • Measurable disease defined as any of the following:
  • Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis.
  • ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum free light chain ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
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  • Received 2-4 prior lines of therapy, including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to both the last line of therapy and to lenalidomide (≥ 10 mg) administered within 18 months prior to randomization. Refractory to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle.
  • Life expectancy of ≥ 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to start of treatment. Participants must agree to ongoing pregnancy testing. All patients must be willing to comply with all requirements of the USA pomalidomide Risk Evaluation and Mitigation Strategy (REMS) program or the pomalidomide Pregnancy Prevention Plan (PPP).
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
  • 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec Fridericia Formula.
  • The following laboratory results must be met during screening and also immediately before study drug administration on Cycle 1 Day 1:
  • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3 (1.0 x 10^9/L)
  • Platelet count ≥ 75,000 cells/mm^3 (75 x 10^9/L)
  • Hemoglobin ≥ 8.0 g/dl
  • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilberts syndrome, that have been reviewed and approved by the medical monitor.
  • Aspartate transaminase (AST /SGOT) and alanine transaminase (ALT/SGPT) ≤ 3.0 x ULN.
  • Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min.
  • Must be able to take antithrombotic prophylaxis.
  • Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC-line], or central venous catheter) (Insertion only required if randomized to Arm A).

Who cannot join

  • Primary refractory disease (i.e. never responded (≥ MR) to any prior therapy)
  • Evidence of mucosal or internal bleeding or platelet transfusion refractory
  • Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
  • Prior exposure to pomalidomide
  • Known intolerance to IMiDs.
  • Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization.
Show all 21Show fewer
  • Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance.
  • Pregnant or breast-feeding females
  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
  • Known human immunodeficiency virus or active hepatitis C viral infection
  • Active hepatitis B viral infection (defined as HBsAg+).
  • Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
  • Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation.
  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome
  • Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to randomization. IMiDs, PIs and or corticosteroids within 2 weeks prior to randomization. Other investigational therapies and monoclonal antibodies within 4 weeks of randomization. Prednisone up to but no more than 10 mg orally q.d. or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to randomization
  • Residual side effects to previous therapy > grade 1 prior to randomization (Alopecia any grade and/or neuropathy grade 2 without pain are permitted)
  • Prior peripheral stem cell transplant within 12 weeks of randomization
  • Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
  • Prior major surgical procedure or radiation therapy within 4 weeks of the randomization
  • Known intolerance to steroid therapy

Trial locations and contacts

105 sites in 21 countries.

105 sites in 21 countries

United States14 sites

  • US16

    Boise, Idaho, 83712

  • US13

    Boston, Massachusetts, 02215

  • US15

    Fort Sam Houston, Texas, 78234

  • US01

    Fresno, California, 93710

  • US11

    Gainesville, Florida, 32610

  • US-27

    Hattiesburg, Mississippi, 39401

  • US-24

    Louisville, Kentucky, 40207

  • US12

    Orange City, Florida, 32763

  • US06

    Philadelphia, Pennsylvania, 19107

  • US-19

    Plantation, Florida, 33324

  • US-21

    Salisbury, North Carolina, 28144

  • US-18

    Temple, Texas, 76504

  • US17

    Tucson, Arizona, 85711

  • US-30

    Winston-Salem, North Carolina, 27103

Other trials in United States

France10 sites

  • FR04

    Brest

  • FR-11

    Cholet

  • FR01

    Le Mans

  • FR05

    Limoges

  • FR-07

    Lyon

  • FR06

    Lyon

  • FR03

    Mulhouse

  • FR-09

    Nice

  • FR-10

    Périgueux

  • FR-08

    Poitiers

Other trials in France

Russia10 sites

  • RU-04

    Izhevsk

  • Ru-11, Ru-14

    Krasnoyarsk

  • RU-03

    Moscow

  • RU-09

    Nizhny Novgorod

  • RU-10

    Novosibirsk

  • RU-06

    Petrozavodsk

  • Ru-01, Ru-02, Ru-08, Ru-12, Ru-14

    Saint Petersburg

  • RU-07

    Samara

  • RU-13

    Syktyvkar

  • RU-05

    Yekaterinburg

Other trials in Russia

Spain9 sites

  • ES11

    Badalona

  • Es02, Es13, Es14

    Barcelona

  • Es01, Es04, Es09

    Madrid

  • ES-15

    Málaga

  • Es07, Es12

    Pamplona

  • ES10

    Salamanca

  • ES03

    Santa Cruz de Tenerife

  • ES08

    Seville

  • Es05, Es06

    Valencia

Other trials in Spain

Italy8 sites

  • IT07

    Bergamo

  • IT02

    Bologna

  • IT08

    Brescia

  • It03, It09

    Milan

  • IT06

    Modena

  • IT04

    Piacenza

  • IT05

    Terni

  • IT01

    Torino

Other trials in Italy

Poland8 sites

  • PL03

    Bialystok

  • PL02

    Chorzów

  • PL06

    Lodz

  • PL05

    Lublin

  • PL-08

    Olsztyn

  • PL07

    Poznan

  • PL04

    Rzeszów

  • PL-09

    Torun

Other trials in Poland

Israel6 sites

  • IL03

    Jerusalem

  • IL01

    Nahariya

  • IL05

    Rehovot

  • IL02

    Safed

  • IL04

    Tel Aviv

  • IL06

    Tel Aviv

Other trials in Israel

Czechia5 sites

  • CZ-05

    Brno

  • CZ-03

    Hradec Králové

  • CZ-04

    Olomouc

  • CZ-01

    Ostrava

  • Cz-02, Cz-06

    Prague

Other trials in Czechia

Taiwan5 sites

  • TW-02

    Chiayi City

  • Tw-04, Tw-07

    Kaohsiung City

  • TW-03

    Taichung

  • TW-05

    Tainan

  • Tw-01, Tw-06

    Taipei

Other trials in Taiwan

Hungary4 sites

  • Hu02, Hu03, Hu04

    Budapest

  • HU01

    Debrecen

  • HU-06

    Kaposvár

  • HU-05

    Pécs

Other trials in Hungary

South Korea4 sites

  • KR-06

    Busan

  • KR-05

    Daegu

  • KR-04

    Hwasun

  • Kr-01, Kr-02, Kr-03

    Seoul

Other trials in South Korea

United Kingdom4 sites

  • GB03

    Liverpool

  • GB01

    Manchester

  • GB02

    Milton Keynes

  • GB04

    Southampton

Other trials in United Kingdom

Belgium3 sites

  • BE-05

    Edegem

  • BE-03

    Liège

  • BE-02

    Roeselare

Other trials in Belgium

Greece3 sites

  • Gr02, Gr03

    Athens

  • GR04

    Pátrai

  • GR01

    Thessaloniki

Other trials in Greece

Austria2 sites

  • AT-02

    Linz

  • AT-01

    Vienna

Other trials in Austria

Estonia2 sites

  • EE-01

    Tallinn

  • EE-02

    Tartu

Other trials in Estonia

Lithuania2 sites

  • LT-02

    Kaunas

  • LT-01

    Vilnius

Other trials in Lithuania

Norway2 sites

  • NO-02

    Ålesund

  • NO01

    Oslo

Other trials in Norway

Romania2 sites

  • RO-02

    Brasov

  • RO-01

    Bucharest

Other trials in Romania

Denmark1 site

  • DK01

    Vejle

Other trials in Denmark

Netherlands1 site

  • NL01

    Rotterdam

Other trials in Netherlands

About this study

Official title: A Randomized, Controlled, Open-label, Phase 3 Study of Melflufen/Dexamethasone Compared With Pomalidomide/Dexamethasone for Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Lenalidomide

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Patients received either melflufen+dex or pomalidomide+dex.

Read the detailed description

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide.

Patients were randomized to either one of two arms:

Arm A: Melphalan flufenamide (Melflufen) 40 mg on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Arm B: Pomalidomide 4 mg daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Patients ≥ 75 years of age received a reduced dose of dexamethasone of 20 mg on Days 1, 8, 15 and 22 for both Arm A and Arm B.

Patients were to receive treatment until such time as there was documented disease progression, unacceptable toxicity, or the patient/treating physician determined it was not in the patient's best interest to continue.

Dose modifications and delays in therapy may have been implemented based on patient tolerability as detailed in the protocol. In the event of a cycle delay, unrelated to dexamethasone toxicity, it was recommended to continue dexamethasone weekly.

Being tested
Melflufen, Pomalidomide, Dexamethasone
Keywords
Refractory Multiple Myeloma, Relapsed Multiple Myeloma, Melphalan flufenamide (Melflufen), Pomalidomide, Dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MelflufenDrug

    Also called Melphalan Flufenamide, Pepaxti

    Intravenous infusion

  • PomalidomideDrug

    Also called Pomalyst, Imnovid

    Oral capsules

  • DexamethasoneDrug

    Also called Dex, Fortecortin, Decadron

    Oral tablets

Study groups in NCT03151811
Study groupRoleWhat they receive
Arm A: Melflufen+DexamethasoneExperimentalMelflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.
Receives: Drug: Melflufen; Drug: Dexamethasone
Arm B: Pomalidomide+DexamethasoneActive comparatorPomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.
Receives: Drug: Pomalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    Progression Free Survival defined as the duration in months from randomization until first evidence of confirmed disease progression, as assessed by the Independent Review Committee (IRC) according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Disease progression was defined according to the IMWG-URC as progressive disease or death due to any cause, whichever occurs first.

    Measured: From date of randomization until first evidence of confirmed disease progression or death due to any cause (whichever occurred first), up to the data cutoff date of 03 Feb 2021 (ie, assessed up to approximately 43 months).

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    ORR defined as the proportion of patients for whom the best overall confirmed response is stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by IRC.

    Measured: From randomization until best response achieved before confirmed disease progression or death due to any cause, up to data cutoff of 03 Feb 2021 (ie, assessed up to approx. 43 months). Median time to best response: Arm A=2.1 months and Arm B=2.0 months

  2. Duration of Response (DOR)

    DOR defined as the duration in months from first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause.

    Measured: From first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause, up to the data cutoff date of 03 Feb 2021 (ie, assessed up to approximately 43 months).

  3. Overall Survival (OS)

    OS defined as the time in months from randomization to date of death due to any cause. Patients who were still alive at end of study, or lost to follow up, were censored at the last day the patient was known to be alive.

    Measured: From date of randomization until up to 24 months following confirmed disease progression or initiation of subsequent therapy, up to the data cutoff date of 03 Feb 2023 (ie, assessed up to approximately 67 months).

  4. Safety and Tolerability: Number of Patients With Treatment-emergent Adverse Events (TEAEs), Including Clinical Laboratory and Vital Signs Abnormalities, as Assessed by CTCAE v4.0

    Number of patients with TEAEs, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 are presented. No formal statistical analysis was performed for safety endpoints.

    Measured: From start of dosing until 30 days after the last dose of study treatment, up to the data cutoff date of 03 Feb 2023 (ie, assessed up to approximately 67 months). Median duration of study treatment was 25.2 and 22.1 weeks for Arm A and B, respectively.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2017
  2. Study start12 Jun 2017
  3. Primary completion3 Feb 2021
  4. Study completion3 Feb 2023

Why it stopped: Sponsor assessed all endpoints and collected Overall Survival data for another two years following the primary completion date of 03Feb2021.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
495 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03151811
Sponsor's protocol ID
OP-103
Acronym
OCEAN
Status last verified
Dec 2023
First submitted
9 May 2017
Last updated
30 Jan 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Acs K, Miettinen JJ, Sergeev P, Heckel T, Diao Y, Witt-Mulder K, Thureson M, Bischler T, Huppunen ME, Suvela M, Obermuller J, Munawar U, Slipicevic A, Bargou RC, Lehmann F, Gelius SS, Norin S, Schjesvold F, Sonneveld P, Stuhmer T, Heckman CA. Efficacy of melflufen in multiple myeloma with mutated or deleted TP53. Exp Hematol Oncol. 2025 Dec 23;14(1):138. doi: 10.1186/s40164-025-00729-1.

    PubMed 41437395

  • Schjesvold FH, Ludwig H, Delimpasi S, Robak P, Coriu D, Tomczak W, Pour L, Spicka I, Dimopoulos MA, Masszi T, Chernova NG, Sandberg A, Thuresson M, Norin S, Bakker NA, Mateos MV, Richardson PG, Sonneveld P. Health-related quality of life in relapsed/refractory multiple myeloma treated with melflufen and dexamethasone: analyses from the phase III OCEAN study. Haematologica. 2024 Jul 1;109(7):2331-2336. doi: 10.3324/haematol.2023.284635. No abstract available.

    PubMed 38426292

  • Sonneveld P, Richardson PG, Ludwig H, Dimopoulos MA, Schjesvold FH, Hajek R, Abdulhaq H, Thuresson M, Norin S, Bakker NA, Mateos MV. Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):687-696. doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.

    PubMed 37355418

  • Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Spicka I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosinol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hajek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. doi: 10.1016/S2352-3026(21)00381-1. Epub 2022 Jan 12.

    PubMed 35032434

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Melflufen, Pomalidomide and Dexamethasone in people with Multiple Myeloma, run by Oncopeptides AB at 105 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 105 sites in United States, France, Russia, Spain, Italy and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: From date of randomization until first evidence of confirmed disease progression or death due to any cause (whichever occurred first), up to the data cutoff date of 03 Feb 2021 (ie, assessed up to approximately 43 months).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03151811, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.

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OCEAN Clinical Trial NCT03151811 | AzTrials