Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Precision For Medicine | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will evaluate melflufen in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma in whose disease is refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. All patients in the study will be treated with melflufen on Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.
Melphalan flufenamide (melflufen) is a peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Peptidases are expressed in several cancers, including solid tumors and hematologic malignancies. Melphalan flufenamide is rapidly taken up by myeloma cells due to its high lipophilicity. Once inside the myeloma cell, the activity of melphalan flufenamide is determined by its immediate cleavage by peptidases into hydrophilic alkylator payloads that are entrapped. Melphalan flufenamide is 50-fold more potent than melphalan in myeloma cells in vitro due to increased intracellular alkylator concentration. It rapidly induces irreversible DNA damage leading to apoptosis of myeloma cells. Melphalan flufenamide displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, in vitro. Melphalan flufenamide also has demonstrated inhibition of angiogenesis and DNA damage with a lack of functional DNA repair in preclinical studies.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| melphalan flufenamide (melflufen) + dexamethasone | Experimental | Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (20 mg for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melphalan flufenamide (Melflufen) | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; <5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h; If only FLC disease, >90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to <200 mg/24 h; other special cases if M-protein unmeasurable | Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 15.3 months. Longest time on treatment 35 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be >10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be >10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Johan Harmenberg, MD, PhD | Oncopeptides AB | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Innovative Clinical Research Institute (ICRI) | Whittier | California | 90603 | United States | ||
| University of Florida |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33296242 | Result | Richardson PG, Oriol A, Larocca A, Blade J, Cavo M, Rodriguez-Otero P, Leleu X, Nadeem O, Hiemenz JW, Hassoun H, Touzeau C, Alegre A, Paner A, Maisel C, Mazumder A, Raptis A, Moreb JS, Anderson KC, Laubach JP, Thuresson S, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Mateos MV; HORIZON (OP-106) Investigators. Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma. J Clin Oncol. 2021 Mar 1;39(7):757-767. doi: 10.1200/JCO.20.02259. Epub 2020 Dec 9. | |
| 37355418 |
Not provided
Not provided
157 Patients were enrolled and treated on study
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set | Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 20, 2020 | Oct 1, 2021 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Dexamethasone |
| Drug |
IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe. |
|
| Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest follow-up time for PFS recorded as 37.2 months at study end. |
| Duration of Response | Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes. | From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time of response recorded as 36.2 months at study end. |
| Overall Survival | Time from start of treatment to death | From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation. |
| Functional Status and Well-being: EORTC QLQ-C30 | Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent. | To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018. |
| Functional Status and Well-being: EQ-5D-3L | Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a "health utility" score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. The EQ VAS scores rates "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual. | To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018. |
| Clinical Benefit Rate | The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories. | Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study treatment recorded as 35.0 months at study end. |
| Time to Response | Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR). | From start of treatment to first confirmed response. Longest time to response in study recorded as 15.3 months. |
| Time to Progression | Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes. | From start of treatment to first evidence of disease progression or date of death from any cause, whichever came first. Longest time to progression recorded was 37.2 months at study end. |
| Gainesville |
| Florida |
| 32610 |
| United States |
| RUSH | Chicago | Illinois | 60612 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Karmanos Cancer Center | Detroit | Michigan | 48201 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Hudson Valley Hematology Oncology | Poughkeepsie | New York | 10532 | United States |
| UPMC Hillman Cancer Insitute | Pittsburgh | Pennsylvania | 15232 | United States |
| Baylor | Dallas | Texas | 75246 | United States |
| CHU de Nantes | Nantes | 44000 | France |
| CHU de Poitiers | Poitiers | 86021 | France |
| Universita di Bolognia | Bologna | 40126 | Italy |
| Turin Hospital Myeloma Unit | Turin | 10126 | Italy |
| Hospital Clinic i Provincial de Barcelona | Barcelona | 08036 | Spain |
| Institut Català d'Oncología (ICO) Badalona | Barcelona | 08916 | Spain |
| Hospital Universitario de La Princesa | Madrid | 28006 | Spain |
| Hospital Universitario Fundación Jiménez Díaz | Madrid | 28040 | Spain |
| Clínica Universidad de Navarra | Pamplona | 31008 | Spain |
| Complejo Hospitalario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Universitario Doctor Peset | Valencia | 46017 | Spain |
| Derived |
| 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. |
| 34671975 | Derived | Larocca A, Leleu X, Touzeau C, Blade J, Paner A, Mateos MV, Cavo M, Maisel C, Alegre A, Oriol A, Raptis A, Rodriguez-Otero P, Mazumder A, Laubach J, Nadeem O, Sandberg A, Orre M, Torrang A, Bakker NA, Richardson PG. Patient-reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study. Br J Haematol. 2022 Feb;196(3):639-648. doi: 10.1111/bjh.17887. Epub 2021 Oct 21. |
| COMPLETED | Study completion for assessment of endpoints |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Melphalan Flufenamide (Melflufen) + Dexamethasone | Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| ECOG Performance Status | ECOG Performance Status Categories Status 0: Normal activity, fully active, able to carry on all pre-disease performance without restriction. Status 1: Symptoms, but fully ambulatory, restricted in physically strenuous but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work). Status 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Status 3: Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. | Count of Participants | Participants |
| |||||||||||||||||
| Weight | Baseline weight not recorded for one patient | Mean | Standard Deviation | kilograms |
| ||||||||||||||||
| International Staging System (ISS) | International Staging System (ISS) is an assessment of risk factors for multiple myeloma ISS Stage I: Serum B2-microglobulin < 3.5 mg/L, serum albumin ≥ 3.5 g/dL ISS Stage II: Not ISS Stage I or III ISS Stage III: Serum B 2-microglobulin ≥ 5.5 mg/L | Count of Participants | Participants |
| |||||||||||||||||
| Time since initial diagnosis | Mean | Standard Deviation | years |
| |||||||||||||||||
| Extramedullary disease at study entry | Count of Participants | Participants |
| ||||||||||||||||||
| Type of measurable disease at baseline | Serum M-protein ≥ 0.5 g/dL (SPEP), urine M-protein ≥ 200 mg/24 hours (UPEP), or serum free light chain (sFLC) assay with FLC ≥ 10 mg/dL (≥ 100 mg/L) and abnormal serum immunoglobulin kappa to lambda FLC ratio. | 5 patients did not have all assessments completed to adequately categorize | Count of Participants | Participants |
| ||||||||||||||||
| Cytogenetic risk group based on FISH at study entry | High-risk cytogenetic abnormalities at study entry is defined as patients who had the genetic subtype t(4; 14), t(14:16), deletion 17p, gain 1q (+1q), or t(14,20) determined by Baseline fluorescence in situ hybridization (FISH) | Count of Participants | Participants |
| |||||||||||||||||
| Heavy-light chain combination at study entry | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Response Rate (ORR) | The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; <5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h; If only FLC disease, >90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to <200 mg/24 h; other special cases if M-protein unmeasurable | Posted | Count of Participants | Participants | Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 15.3 months. Longest time on treatment 35 months. |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) | Time from start of treatment to either progression or death, whichever comes first as assessed by the investigator using IMWG criteria. Progression of disease is defined by an increase of 25% from the lowest response for either of Serum M-component (absolute increase of ≥ 0.5 g/dL) or Urine M-component (absolute increase of ≥200 mg/ 24h); In patients without measurable M-protein a 25% increase in the difference between involved and uninvolved FLC (free light chain) levels (absolute increase must be >10 mg/dL); If unmeasurable FLC levels, a 25% increase in bone marrow plasma cell percentage (absolute percentage must be >10%); New bone or soft tissue plasmacytomas or definite increase in existing ones; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder | Full analysis set | Posted | Median | 95% Confidence Interval | months | Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest follow-up time for PFS recorded as 37.2 months at study end. |
| |||||||||||||||||||||||||||||||||
| Secondary | Duration of Response | Time from first response to progression based on investigator assessment. See definitions of response and progression in ORR and PFS outcomes. | Patients with a best response of PR or better as determined by the investigator. | Posted | Median | 95% Confidence Interval | months | From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time of response recorded as 36.2 months at study end. |
| |||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Time from start of treatment to death | Full Analysis Set. | Posted | Median | 95% Confidence Interval | months | From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation. |
| |||||||||||||||||||||||||||||||||
| Secondary | Functional Status and Well-being: EORTC QLQ-C30 | Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30. The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales, 1 Global Health Status scale, 3 symptom scales, and 6 single items. The recall period is 1 week (the past week). The scales are transformed to a 0 (worst) to 100 (best) scale. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better HRQoL. If at least 50% of the items from the scale had been answered, the missing items were assumed to have values equal to the average of those items which were present for that respondent. | This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease. 62 pts in the FAS included after QoL was added in Amd 4, whereof 48 pts in the sub-group of pts with TCR disease. This outcome measure was not analyzed/reported separately for the sub-group of patients with EMD as there were limited no. of pts with EMD among the QoL patients. No data/results are available to report for patients with EMD. | Posted | Mean | Standard Deviation | units on a scale | To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018. |
| |||||||||||||||||||||||||||||||||
| Secondary | Functional Status and Well-being: EQ-5D-3L | Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L. The EQ-5D-3L questionnaire converts 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression of patient-reported, current-day health status into a "health utility" score. For the EQ-5D-3L questionnaire, each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. The EQ VAS scores rates "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No imputation of missing items or composite scores were done. The scores for the 5 dimensions are used to compute a single utility score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual. | This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease. 62 pts in the FAS included after QoL was added in Amd 4, whereof 48 pts in the sub-group of pts with TCR disease. This outcome measure was not analyzed/reported separately for the sub-group of patients with EMD as there were limited no. of pts with EMD among the QoL patients. No data/results are available to report for patients with EMD. | Posted | Mean | Standard Deviation | Change in composite scale score | To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018. |
| |||||||||||||||||||||||||||||||||
| Secondary | Clinical Benefit Rate | The clinical benefit rate (CBR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, PR, or MR as their best response as assessed by the investigator. See Primary Outcome (ORR) for definitions of response categories. | Posted | Count of Participants | Participants | Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time on study treatment recorded as 35.0 months at study end. |
| |||||||||||||||||||||||||||||||||||
| Secondary | Time to Response | Duration from start of treatment to the first occurrence of a confirmed response of PR or better as assessed by the investigator. See definitions of response in Primary Outcome (ORR). | This outcome measure was pre-specified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and "Mel + Dex: Patients With TCR Disease. This outcome measure was analyzed/reported for patients with a best response of PR or better in the full analysis set as well as in the sub-group of patients with triple class refractory disease. This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients. | Posted | Median | Full Range | months | From start of treatment to first confirmed response. Longest time to response in study recorded as 15.3 months. |
| |||||||||||||||||||||||||||||||||
| Secondary | Time to Progression | Duration from start of treatment to first evidence of disease progression as assessed by the investigator. See definitions of response and progression in ORR and PFS outcomes. | This outcome measure was prespecified to be analyzed/reported for the Mel + Dex: FAS Arm/Group and Mel + Dex: Patients With TCR Disease. This outcome measure was analyzed/reported for patients in the full analysis set as well as in the sub-group of patients with triple class refractory disease. This outcome measure was not analyzed/reported separately for the sub-group of patients with Extramedullary Disease. No data available to report for EMD patients. | Posted | Median | 95% Confidence Interval | months | From start of treatment to first evidence of disease progression or date of death from any cause, whichever came first. Longest time to progression recorded was 37.2 months at study end. |
|
Patients were treated in 28 day cycles indefinitely until withdrawal from study, with the longest time on study of 17 months. Adverse events were collected until 30 days after the last dose of study drug. Patients were followed for survival for 24 months after disease progression or start of subsequent anti-myeloma therapy.
The Safety Analysis Set for evaluation of adverse events included all patients who received at least one dose of melflufen or dexamethasone in the study. Patients that were triple-class refractory and those with extramedullary disease were defined as a subgroups of interest for evaluation.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Full Analysis Set | Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle. Melphalan flufenamide (Melflufen) Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe. | 130 | 157 | 88 | 157 | 157 | 157 |
| EG001 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease | Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass. | 51 | 55 | 38 | 55 | 55 | 55 |
| EG002 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease | Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody. | 105 | 119 | 70 | 119 | 119 | 119 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Bronchitis viral | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Escherichia sepsis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Fungal sepsis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Lower respiratory infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Pneumonia viral | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Methaemoglobinaemia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Diffuse alveolar damage | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Nephropathy | Renal and urinary disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Metabolic disorder | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cardiac amyloidosis | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cardiopulmonary failure | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Plasma cell leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Plasma cell myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hyperammonaemic encephalopathy | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Pneumonia pneumococcal | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Pneumonia influenzal | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Extradural haematoma | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
| |
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Refractory cytopenia with multilineage dysplasia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cerecrovascular accident | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 19.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 19.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 19.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Project Lead | Oncopeptides | 866-596-6626 | info@oncopeptides.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 18, 2020 | Aug 23, 2022 | SAP_002.pdf |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C482580 | L-melphalanyl-p-L-fluorophenylalanine ethyl ester |
| C585069 | melflufen |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
Not provided
Not provided
| >=65 years |
|
|
| Unknown or Not Reported |
|
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| France |
|
|
| Spain |
|
|
| Performance Status 1 |
|
| Performance Status 2 |
|
| Performance Status 3 |
|
| International Staging System (ISS) Stage II |
|
| International Staging System (ISS) Stage III |
|
| Unknown |
|
| Missing |
|
| SPEP only |
|
|
| UPEP only |
|
|
| sFLC only |
|
|
| Unable to determine |
|
|
| Standard |
|
| Unknown |
|
|
| IgD-Kappa |
|
| IgD-Lambda |
|
| IgG-Kappa |
|
| IgG-Lambda |
|
| IgM-Kappa |
|
| Multiple-Kappa |
|
| None-Kappa |
|
| None-Lambda |
|
| Unknown-Kappa |
|
| Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Extramedullary Disease |
Patients with extramedullary disease at baseline defined as myeloma disease either originating in, but extending beyond, the cortical bone or as a separate soft tissue mass |
| OG002 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease | Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody |
|
|
Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody |
|
|
|
|
| OG001 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease | Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody |
|
|
Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.
Melphalan flufenamide (Melflufen)
Dexamethasone: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.
| OG001 | Melphalan Flufenamide (Melflufen) + Dexamethasone: Patients With Triple Class Refractory Disease | Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody |
|
|
Triple class refractory population defined as refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody
|
|
|
|
|
|