Clinical Trials List
Protocol NumberOP-103
NCT Number(ClinicalTrials.gov Identfier)NCT03151811
Completed
2019-07-15 - 2022-12-31
Phase III
Recruiting7
ICD-10C90.00
Multiple myeloma not having achieved remission
ICD-10C90
Multiple myeloma and malignant plasma cell neoplasms
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
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Trial Applicant
TAIWAN PSI HEALTH DEVELOPMENT COMPANY LIMITED
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Sponsor
Oncopeptides AB
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Tzeon-jye Chiou Division of Hematology & Oncology
- Jyh-Pyng Gau Division of Hematology & Oncology
- Hao-Yuan Wang Division of Hematology & Oncology
- Po-Shen Ko Division of Hematology & Oncology
- Liang-Tsai Hsiao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蘇裕傑 Division of Hematology & Oncology
- 張肇松 Division of Hematology & Oncology
- Sheng-Fung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tzu-Ting Chen Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 田豐銘 Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 徐思淳 Division of Hematology & Oncology
- BANG-BIN CHEN Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- 林耘曲 Division of Hematology & Oncology
- Tai-Chung Huang 未分科
- Shang-Ju Wu Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- RUOH-FANG YEN 未分科
- - - Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- NAI-HSIN CHI Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Yi-Chang Liu Division of Hematology & Oncology
- Shih-Feng Cho Division of Hematology & Oncology
- Hui-Ching Wang Division of Hematology & Oncology
- 唐世豪 Division of Hematology & Oncology
- Jeng-Shiun Du Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
復發性頑固型多發性骨髓瘤
Objectives
PRIMARY OBJECTIVES
To compare the PFS of melflufen plus dexamethasone (Arm A) versuspomalidomide plus dexamethasone (Arm B) as assessed by the IndependentReview Committee (IRC) according to the International Myeloma WorkingGroup Uniform Response Criteria (IMWG-URC) (Rajkumar et al. 2011,Appendix C).Key Secondary Objectives
To assess and compare the overall response rate (ORR), i.e., proportion ofpatients with ≥ PR (stringent complete response [sCR], complete response[CR], very good partial response [VGPR] and partial response [PR]) as bestresponse in Arm A versus Arm B
To assess and compare duration of response (DOR) in patients with ≥ PR (sCR,CR, VGPR, PR) as best response in Arm A versus Arm B
To assess and compare overall survival (OS) in Arm A versus Arm B To assess and compare the safety and tolerability in Arm A and Arm B
Test Drug
Melflufen
Active Ingredient
Melphalan flufenamide hydrochloride/ 20mg
Dosage Form
powder
Dosage
20mg
Endpoints
Primary Outcome Measures :
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)
Secondary Outcome Measures :
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.
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)
Secondary Outcome Measures :
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.
Inclution Criteria
Inclusion Criteria:
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).
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).
Exclusion Criteria
Exclusion Criteria:
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
POEMS syndrome
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
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
POEMS syndrome
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
The Estimated Number of Participants
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Taiwan
22 participants
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Global
450 participants
