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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT03151811
• Date of registration: 09/05/2017
• Prospective Registration: Yes
• Primary sponsor: Oncopeptides AB
• Public title: A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide OCEAN
• Scientific 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
• Date of first enrolment: June 12, 2017
• Target sample size: 495
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03151811
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: Pieter Sonneveld, Prof.
• Affiliation: Erasmus Medical Center

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Pomalidomide

Drug: Melflufen

Drug: Dexamethasone

Primary Outcome(s)

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 Outcome(s)

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]

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).]

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.]

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).]

Secondary ID(s)

OP-103

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/07/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03151811