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

Sponsor
Oncopeptides AB (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03151811
Collaborator
(none)
495
Enrollment
105
Locations
2
Arms
86.7
Anticipated Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients with RRMM following 2-4 lines of prior therapy and who are 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 will receive either melflufen+dex or pomalidomide+dex.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients with RRMM following 2-4 lines of prior therapy and who are 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 will be 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 will have a reduced dose of dexamethasone of 20 mg on Days 1, 8, 15 and 22 for both Arm A and Arm B.

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

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

Study Design

Study Type:
Interventional
Actual Enrollment :
495 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 12, 2017
Anticipated Primary Completion Date :
Dec 3, 2021
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A: Melflufen+Dexamethasone

Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle. Patients are to be treated until confirmed progression, unacceptable toxicity or the patient or investigator decides it is not in the patients best interest to continue.

Drug: Melflufen
Intravenous infusion
Other Names:
  • Melphalan Flufenamide
  • Drug: Dexamethasone
    Oral tablets
    Other Names:
  • Dex
  • Fortecortin
  • Decadron
  • Active Comparator: Arm B: Pomalidomide+Dexamethasone

    Pomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle. Patients are to be treated until confirmed progression, unacceptable toxicity or the patient or investigator decides it is not in the patients best interest to continue.

    Drug: Pomalidomide
    Oral capsules
    Other Names:
  • Pomalyst
  • Imnovid
  • Drug: Dexamethasone
    Oral tablets
    Other Names:
  • Dex
  • Fortecortin
  • Decadron
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [From randomization to time of progression, or, if no progression, 24 months after end of treatment]

      To compare the PFS of melflufen plus dexamethasone (Arm A) versus pomalidomide plus dexamethasone (Arm B) as assessed by the Independent Review Committee (IRC) according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [From randomization until best response achieved before confirmed progression, or if no progression, 24 months after end of treatment]

      To assess and compare the ORR in Arm A versus Arm B

    2. Duration of Response (DOR) [From first evidence of response until confirmed progression, or if no progression, 24 months after end of treatment]

      To assess and compare the DOR in Arm A versus Arm B

    3. Overall Survival (OS) [From randomization until end of study (2 years after confirmed progression)]

      To assess and compare OS in Arm A versus Arm B

    4. Safety and Tolerability: Number of patients with treatment-emergent adverse events, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 [From start of dosing until 30 days after last dose]

      To assess and compare safety and tolerability in Arm A versus Arm B. Number of patients with treatment-emergent adverse events, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 will be presented. No formal statistical analysis will be performed for safety endpoints.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male or female, age 18 years or older

    2. A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening

    3. 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

    1. 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.

    2. Life expectancy of ≥ 6 months

    3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

    4. 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).

    5. Ability to understand the purpose and risks of the study and provide signed and dated informed consent.

    6. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec Fridericia Formula.

    7. 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/mm3 (1.0 x 109/L)

    • Platelet count ≥ 75,000 cells/mm3 (75 x 109/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.

    1. Must be able to take antithrombotic prophylaxis.

    2. 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).

    Exclusion Criteria:
    1. Primary refractory disease (i.e. never responded (≥ MR) to any prior therapy)

    2. Evidence of mucosal or internal bleeding or platelet transfusion refractory

    3. 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.

    4. Prior exposure to pomalidomide

    5. Known intolerance to IMiDs.

    6. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization.

    7. 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.

    8. Pregnant or breast-feeding females

    9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation

    10. Known human immunodeficiency virus or active hepatitis C viral infection

    11. 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.

    1. Concurrent symptomatic amyloidosis or plasma cell leukemia

    2. POEMS syndrome

    3. 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

    4. Residual side effects to previous therapy > grade 1 prior to randomization (Alopecia any grade and/or neuropathy grade 2 without pain are permitted)

    5. Prior peripheral stem cell transplant within 12 weeks of randomization

    6. Prior allogeneic stem cell transplantation with active graft-versus-host-disease.

    7. Prior major surgical procedure or radiation therapy within 4 weeks of the randomization

    8. Known intolerance to steroid therapy

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1US17TucsonArizonaUnited States85711
    2US01FresnoCaliforniaUnited States93710
    3US11GainesvilleFloridaUnited States32610
    4US12Orange CityFloridaUnited States32763
    5US-19PlantationFloridaUnited States33324
    6US16BoiseIdahoUnited States83712
    7US-24LouisvilleKentuckyUnited States40207
    8US13BostonMassachusettsUnited States02215
    9US-27HattiesburgMississippiUnited States39401
    10US-21SalisburyNorth CarolinaUnited States28144
    11US-30Winston-SalemNorth CarolinaUnited States27103
    12US06PhiladelphiaPennsylvaniaUnited States19107
    13US15Fort Sam HoustonTexasUnited States78234
    14US-18TempleTexasUnited States76504
    15AT-02LinzAustria
    16AT-01ViennaAustria
    17BE-05EdegemBelgium
    18BE-03LiègeBelgium
    19BE-02RoeselareBelgium
    20CZ-05BrnoCzechia
    21CZ-03Hradec KrálovéCzechia
    22CZ-04OlomoucCzechia
    23CZ-01OstravaCzechia
    24Cz-02, Cz-06PrahaCzechia
    25DK01VejleDenmark
    26EE-01TallinnEstonia
    27EE-02TartuEstonia
    28FR04BrestFrance
    29FR-11CholetFrance
    30FR01Le MansFrance
    31FR05LimogesFrance
    32FR-07LyonFrance
    33FR06LyonFrance
    34FR03MulhouseFrance
    35FR-09NiceFrance
    36FR-08PoitiersFrance
    37FR-10PérigueuxFrance
    38Gr02, Gr03AthensGreece
    39GR04PátraGreece
    40GR01ThessaloníkiGreece
    41Hu02, Hu03, Hu04BudapestHungary
    42HU01DebrecenHungary
    43HU-06KaposvárHungary
    44HU-05PécsHungary
    45IL03JerusalemIsrael
    46IL01NahariyaIsrael
    47IL05ReẖovotIsrael
    48IL02SafedIsrael
    49IL04Tel AvivIsrael
    50IL06Tel AvivIsrael
    51IT07BergamoItaly
    52IT02BolognaItaly
    53IT08BresciaItaly
    54It03, It09MilanoItaly
    55IT06ModenaItaly
    56IT04PiacenzaItaly
    57IT05TerniItaly
    58IT01TorinoItaly
    59KR-06BusanKorea, Republic of
    60KR-05DaeguKorea, Republic of
    61KR-04HwasunKorea, Republic of
    62Kr-01, Kr-02, Kr-03SeulKorea, Republic of
    63LT-02KaunasLithuania
    64LT-01VilniusLithuania
    65NL01RotterdamNetherlands
    66NO01OsloNorway
    67NO-02ÅlesundNorway
    68PL03BiałystokPoland
    69PL02ChorzówPoland
    70PL05LublinPoland
    71PL-08OlsztynPoland
    72PL07PoznańPoland
    73PL04RzeszówPoland
    74PL-09ToruńPoland
    75PL06ŁódźPoland
    76RO-02BraşovRomania
    77RO-01BucharestRomania
    78RU-05EkaterinburgRussian Federation
    79RU-04IzhevskRussian Federation
    80Ru-11, Ru-14KrasnoyarskRussian Federation
    81RU-03MoscowRussian Federation
    82RU-09Nizhny NovgorodRussian Federation
    83RU-10NovosibirskRussian Federation
    84RU-06PetrozavodskRussian Federation
    85Ru-01, Ru-02, Ru-08, Ru-12, Ru-14Saint PetersburgRussian Federation
    86RU-07SamaraRussian Federation
    87RU-13SyktyvkarRussian Federation
    88ES11BadalonaSpain
    89Es02, Es13, Es14BarcelonaSpain
    90Es01, Es04, Es09MadridSpain
    91ES-15MálagaSpain
    92Es07, Es12PamplonaSpain
    93ES10SalamancaSpain
    94ES03Santa Cruz de TenerifeSpain
    95ES08SevillaSpain
    96Es05, Es06ValenciaSpain
    97TW-02Chiayi CityTaiwan
    98Tw-04, Tw-07KaohsiungTaiwan
    99TW-03TaichungTaiwan
    100TW-05TainanTaiwan
    101Tw-01, Tw-06TaipeiTaiwan
    102GB03LiverpoolUnited Kingdom
    103GB01ManchesterUnited Kingdom
    104GB02Milton KeynesUnited Kingdom
    105GB04SouthamptonUnited Kingdom

    Sponsors and Collaborators

    • Oncopeptides AB

    Investigators

    • Principal Investigator: Pieter Sonneveld, Prof., Erasmus Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Oncopeptides AB
    ClinicalTrials.gov Identifier:
    NCT03151811
    Other Study ID Numbers:
    • OP-103
    First Posted:
    May 12, 2017
    Last Update Posted:
    Nov 18, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Oncopeptides AB
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 18, 2021