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NCT03151811 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE3
Status at capture
TERMINATED
Registry last update
2024-01-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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 4. 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. 5. Life expectancy of ≥ 6 months 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 7. 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). 8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent. 9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec Fridericia Formula. 10. 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. 11. Must be able to take antithrombotic prophylaxis. 12. 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. 12. Concurrent symptomatic amyloidosis or plasma cell leukemia 13. POEMS syndrome 14. 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 15. Residual side effects to previous therapy \> grade 1 prior to randomization (Alopecia any grade and/or neuropathy grade 2 without pain are permitted) 16. Prior peripheral stem cell transplant within 12 weeks of randomization 17. Prior allogeneic stem cell transplantation with active graft-versus-host-disease. 18. Prior major surgical procedure or radiation therapy within 4 weeks of the randomization 19. Known intolerance to steroid therapy
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Melflufen 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.
    intervention Names
    1. Drug: Melflufen
    2. Drug: Dexamethasone
    label
    Arm A: Melflufen+Dexamethasone
    type
    EXPERIMENTAL
  2. description
    Pomalidomide 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.
    intervention Names
    1. Drug: Pomalidomide
    2. Drug: Dexamethasone
    label
    Arm B: Pomalidomide+Dexamethasone
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Arm A: Melflufen+Dexamethasone
    description
    Intravenous infusion
    name
    Melflufen
    other Names
    1. Melphalan Flufenamide
    2. Pepaxti
    type
    DRUG
  2. arm Group Labels
    1. Arm B: Pomalidomide+Dexamethasone
    description
    Oral capsules
    name
    Pomalidomide
    other Names
    1. Pomalyst
    2. Imnovid
    type
    DRUG
  3. arm Group Labels
    1. Arm A: Melflufen+Dexamethasone
    2. Arm B: Pomalidomide+Dexamethasone
    description
    Oral tablets
    name
    Dexamethasone
    other Names
    1. Dex
    2. Fortecortin
    3. Decadron
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
SINGLE
who Masked
  1. OUTCOMES_ASSESSOR
primary Purpose
TREATMENT
Enrollment
count
495
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    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).
secondary Outcomes
  1. description
    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.
    measure
    Overall Response Rate (ORR)
    time Frame
    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. description
    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.
    measure
    Duration of Response (DOR)
    time Frame
    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. description
    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.
    measure
    Overall Survival (OS)
    time Frame
    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. description
    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.
    measure
    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
    time Frame
    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.
Full study description
brief 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. Patients received either melflufen+dex or pomalidomide+dex.
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.
Source references
references
  1. citation
    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.
    pmid
    41437395
    type
    DERIVED
  2. citation
    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.
    pmid
    38426292
    type
    DERIVED
  3. citation
    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.
    pmid
    37355418
    type
    DERIVED
  4. citation
    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.
    pmid
    35032434
    type
    DERIVED
Source notices and limitations
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    Preserved source evidence · Not medical advice