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

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ClinicalTrials.gov Identifier: NCT03151811
Recruitment Status : Active, not recruiting
First Posted : May 12, 2017
Last Update Posted : September 18, 2020
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

Tracking Information
First Submitted Date  ICMJE May 9, 2017
First Posted Date  ICMJE May 12, 2017
Last Update Posted Date September 18, 2020
Actual Study Start Date  ICMJE June 12, 2017
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
Progression Free Survival (PFS) [ Time Frame: 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
  • Overall Response Rate (ORR) [ Time Frame: 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
  • Duration of Response (DOR) [ Time Frame: 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
  • Overall Survival (OS) [ Time Frame: From randomization until end of study (2 years after confirmed progression) ]
    To assess and compare OS in Arm A versus Arm B
  • Safety and Tolerability: Number of patients with treatment-emergent adverse events, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Melflufen
    Intravenous infusion
    Other Name: Melphalan Flufenamide
  • Drug: Pomalidomide
    Oral capsules
    Other Names:
    • Pomalyst
    • Imnovid
  • Drug: Dexamethasone
    Oral tablets
    Other Names:
    • Dex
    • Fortecortin
    • Decadron
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Melflufen
    • Drug: Dexamethasone
  • 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.
    Interventions:
    • Drug: Pomalidomide
    • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 17, 2020)
495
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2017)
450
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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/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.
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Czechia,   Denmark,   Estonia,   France,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Netherlands,   Norway,   Poland,   Romania,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03151811
Other Study ID Numbers  ICMJE OP-103
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party Oncopeptides AB
Study Sponsor  ICMJE Oncopeptides AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pieter Sonneveld, Prof. Erasmus Medical Center
PRS Account Oncopeptides AB
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP