OCEAN: A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide
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 Disease||Intervention/Treatment||Phase|
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.
Arms and Interventions
|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.
|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.
Primary Outcome Measures
- 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
- 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
- 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
- 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
- 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.
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
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/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.
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).
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.
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
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
Contacts and Locations
|4||US12||Orange City||Florida||United States||32763|
|10||US-21||Salisbury||North Carolina||United States||28144|
|11||US-30||Winston-Salem||North Carolina||United States||27103|
|13||US15||Fort Sam Houston||Texas||United States||78234|
|41||Hu02, Hu03, Hu04||Budapest||Hungary|
|59||KR-06||Busan||Korea, Republic of|
|60||KR-05||Daegu||Korea, Republic of|
|61||KR-04||Hwasun||Korea, Republic of|
|62||Kr-01, Kr-02, Kr-03||Seul||Korea, Republic of|
|80||Ru-11, Ru-14||Krasnoyarsk||Russian Federation|
|82||RU-09||Nizhny Novgorod||Russian Federation|
|85||Ru-01, Ru-02, Ru-08, Ru-12, Ru-14||Saint Petersburg||Russian Federation|
|89||Es02, Es13, Es14||Barcelona||Spain|
|90||Es01, Es04, Es09||Madrid||Spain|
|94||ES03||Santa Cruz de Tenerife||Spain|
|104||GB02||Milton Keynes||United Kingdom|
Sponsors and Collaborators
- Oncopeptides AB
- Principal Investigator: Pieter Sonneveld, Prof., Erasmus Medical Center
Study Documents (Full-Text)None provided.