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PharmaMar has decided to end this study due to the slow recruitment rate of the trial
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This is a multi-center, open-label, single arm, non-comparative phase II trial, designed to evaluate the efficacy of plitidepsin in combination with bortezomib and dexamethasone in patients with Multiple Myeloma (MM) double refractory to bortezomib and lenalidomide.
This is a multi-center, open-label, single arm, non-comparative phase II trial, designed to evaluate the efficacy of plitidepsin in combination with bortezomib and dexamethasone in patients with MM double refractory to bortezomib and lenalidomide.The primary endpoint will be overall response rate (ORR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR).
Approximately 64 evaluable patients will be needed for the evaluation of the primary endpoint, ORR.
An early futility analysis will be performed with the efficacy data collected from the first 20 evaluable patients. The futility analysis will commence once patient number 20 has completed two full treatment cycles. Patient recruitment will not be halted during the conduct of this futility analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental | Experimental | Plitidepsin + bortezomib + dexamethasone Plitidepsin will be administered as a 3-hour intravenous (i.v.) infusion on Day(D) 1 and 15 , every four weeks (q4wk) Bortezomib will be administered as a bolus subcutaneous (s.c.) injection on D 1, 4, 8 and 11,q4wk Dexamethasone will be taken orally on D1,8,15 and 22, q4wk |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| plitidepsin | Drug | Patients received plitidepsin as a 3-hour i.v. infusion at a dose of 5 mg/m2 on Days 1 and 15 every Four Weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response | Partial response (PR): ≥50% reduction in serum M-protein and reduction of 24-hour urine M-protein by 90% or to <200 mg/24h Minimal response (MR): ≥25% but ≤49% reduction of serum M-protein and reduction of 24h urine M-protein 50-89%. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions Stable disease (SD): not meet the criteria for PR, MR or PD Primary analysis should have been done once a total of 64 patients have received plitidepsin+BTZ+DXM with one futility analysis planned after the inclusion of 20 evaluable patients that had completed two full treatment cycles. Only 10 patients were treatedand 8 evaluable for the primary endpoint (ORR according to IMWG criteria). As a result of slow patient accrual, the study was closed before reaching the target enrollment | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
| Overall Response Rate | The primary endpoint was overall response rate (ORR) (including stringent complete response [sCR], complete response [CR], very good partial response [VGPR] and partial response [PR]), according to the IMWG response criteria. | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Benefit Rate | Clinical benefit rate defined as minimal response or better | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
| Disease Control Rate |
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Inclusion Criteria:
Patients must give written informed consent (IC) in accordance with institutional and local guidelines.
Age ≥ 18 years.
Patients must have a confirmed diagnosis of MM according to the Durie and Salmon criteria.
Patients must have measurable disease defined as any of the following:
Prior autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT) patients are allowed. Patients must not have acute/chronic graft-versus-host disease (GVHD) or be receiving immunosuppressive therapy at least 90 days before the onset of treatment with the trial drug(s).
Patients must have received previous treatment with bortezomib and lenalidomide and be refractory to both.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
Recovery to grade ≤ 1 from any non-hematological adverse event (AE) derived from previous treatment (if present, alopecia and peripheral neuropathy must be grade <1).
Laboratory data:
Evidence of non-childbearing status for women of childbearing potential (WOCBP): WOCBP must have a negative serum or urine pregnancy test within seven days prior to enrolment and must agree to use a highly effective contraceptive measure throughout the trial and during six months after treatment discontinuation. Male patients enrolled in the study should also use contraceptive methods during and after treatment discontinuation.
Left ventricular ejection fraction (LVEF) ≥ 45%.
Patients must have a BM assessment within three weeks prior to enrolment.
Exclusion Criteria:
Previous treatment with plitidepsin.
Active or metastatic primary malignancy other than MM.
Serious concomitant systemic disorders that would compromise the safety of the patient or the patient's ability to complete the trial, including the following specific conditions:
Other relevant cardiac conditions:
History of hypersensitivity reactions and/or intolerance to bortezomib, polyoxyl 35 castor oil, mannitol, boron or dexamethasone.
Myopathy or any clinical situation that causes significant and persistent elevation of creatine phosphokinase (CPK) (> 2.5 ULN) in two different determinations performed within one week of each other.
Grade ≥ 1 neuropathy (either bortezomib-related or not) according to NCI-CTCAE v4.0.
Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patients' participation in this trial.
Pregnant and/or lactating women.
Known active human immunodeficiency virus (HIV) infection (HIV testing is not required unless infection is clinically suspected).
Active hepatitis B or C virus (HBV or HCV) infection.
Treatment with any Investigational Medicinal Product (IMP) in the 30 days before inclusion in the trial.
Concomitant medications that include corticosteroids, chemotherapy (CT), or other therapy that is or may be active against myeloma. Concurrent corticosteroids are allowed as an equivalent to a prednisone dose of ≤ 10 mg daily, administered as an antiemetic or as premedication for blood products.
Wash-out periods after the end of the previous therapy:
Plasma cell leukemia at the time of trial entry.
Disease-related symptomatic hypercalcemia despite optimal medical therapy.
Limitation of the patient's ability to comply with the treatment or follow-up protocol.
Contraindication to use steroids.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de Lille - Hôpital Claude Huriez | Lille | 59037 | France | |||
| Institut Gustave Roussy |
IC signed;Age≥18 years;confirmed diagnosis of MM,ECOG PS≤2;LVEF≥45%;negative pregnancy test
Patients participated between 15May2017 - 30Jul2018 (last follow-up cutoff date). The 1st dose/1st cycle was administered on 15May2017 and the last dose/last cycle on 23Jul2018. At cutoff date 10 patients had been included and treated with plitidepsin+BTZ+DXM and they were evaluable for safety. 8 of these were evaluable for the efficacy endpoint
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental | Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, every four weeks (q4wk); BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated q4wk. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 10, 2015 | Jul 23, 2020 |
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| Bortezomib | Drug | BTZ as a 3-5 second bolus s.c. injection at a dose of 1.3 mg/m2 on Days 1, 4, 8 and 11 every four weeks |
|
| Dexamethasone | Drug | DXM orally at a dose of 40 mg/day on Days 1, 8, 15 and 22 every four weeks |
|
Disease control rate defined as stable disease [SD] or better
| From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
| Duration of Response | Duration of Response defined as the time, in months, from the date of first documentation of response to the date of disease progression. Response was assessed according to the IMWG classification response criteria. | From the date of first documentation of response to the date of disease progression, up to 100 weeks |
| Time to Progression | Time to progression (TTP) was defined as the time, in months, from the date of the first infusion to the date of documented PD or death due to PD. TTP was to be censored on the date of the last tumor assessment or on the date of the first drug administration if there were no tumor assessments. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of the first infusion to the date of documented PD or death due to PD, up to 100 weeks |
| Percentage of Participants With Progression Disease at 3 Months | Progression disease was defined as documented PD or death due to PD Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of the first infusion to the date of documented PD or death due to PD, up to 3 months |
| Percentage of Participants With Progression Disease at 6 Months | Progression disease was defined as documented PD or death due to PD. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions | From the date of the first infusion to the date of documented PD or death due to PD, up to 6 months |
| Percentage of Participants With Progression Disease at 12 Months | Progression disease was defined as documented PD or death due to PD. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of the first infusion to the date of documented PD or death due to PD, up to 12 months |
| Progression-free Survival | Progression-free survival (PFS) was defined as the time, in months, from the date of first drug administration to the date of documented PD, or death (of any cause). If any patient was lost to follow-up before PD or received another antitumor therapy, PFS was to be censored on the date of the last tumor assessment. If there were no tumor assessments, these parameters were to be censored on the date of the first drug administration. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 100 weeks |
| Percentage of Participants With Progression-free Survival at 3 Months | Progression-free Survival was defined as documented PD, or death of any cause. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 3 months |
| Percentage of Participants With Progression-free Survival at 6 Months | Progression-free Survival was defined as documented PD, or death of any cause. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 6 months |
| Percentage of Participants With Progression-free Survival at 12 Months | Progression-free survival (PFS) was defined as the time, in months, from the date of first drug administration to the date of documented PD, or death (of any cause). If any patient was lost to follow-up before PD or received another antitumor therapy, PFS was to be censored on the date of the last tumor assessment. If there were no tumor assessments, these parameters were to be censored on the date of the first drug administration Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 12 months |
| Event-free Survival | Event-free survival (EFS) was defined as the time, in months, from the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death. The censoring rules defined above for PFS were used for EFS | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 100 weeks |
| Percentage of Participants With Event-free Survival at 3 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. rogressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 3 months |
| Percentage of Participants With Event-free Survival at 6 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 6 months |
| Percentage of Participants With Event-free Survival at 12 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 12 months |
| Overall Survival | Overall survival (OS) was defined as the time, in months, from the date of first drug administration to the date of death (of any cause) or last patient contact (in this case, survival was to be censored on that date). | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 100 weeks |
| Percentage of Participants With Overall Survival at 6 Months | Overall survival (OS) was defined as death of any cause. | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 6 months |
| Percentage of Participants With Overall Survival at 12 Months | Overall survival (OS) was defined as death of any cause. | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 12 months |
| Villejuif |
| 94800 |
| France |
| Policlinico Vittorio Emanuele Hospital | Catania | 95123 | Italy |
| Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Meldola | 47014 | Italy |
| Azienda Ospedaliera Città della Salute e della Scienza di Torino | Torino | 00126 | Italy |
| Hospital Universitario Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain |
| Clinica Universidad de Navarra | Pamplona | Navarre | 31008 | Spain |
| Institut Català d´Oncologia Girona | Girona | 17007 | Spain |
| Institut Català d´Oncologia L´Hospitalet | L'Hospitalet de Llobregat | 08908 | Spain |
| Hospital General Universitario J.M. Morales Meseguer | Murcia | 30008 | Spain |
| Hospital Universitario de Salamanca | Salamanca | 37007 | Spain |
| Complexo Hospitalario Universitario de Santiago | Santiago de Compostela | 15706 | Spain |
| Complejo Hospitalario Regional Virgen Del Rocio | Seville | 41013 | Spain |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental | Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, every four weeks (q4wk); BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated q4wk. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| ECOG PS | ECOG PS, Eastern Cooperative Oncology Group performance status PS 0 Fully active able to carry on all pre-disease performance without restriction PS 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature PS 2 Ambulatory and capable of all selfcare but unable to carry out any work activities up and about more than 50% of waking hours PS 3 Capable of only limited selfcare confined to bed or chair more than 50% of waking hours PS 4 Completely disabled cannot carry on any selfcare; totally confined to bed or chair PS 5 Dead | Count of Participants | Participants |
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| Multiple myeloma type at diagnosis | Count of Participants | Participants |
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| Durie-Salmon stage and subclassification at diagnosis | 4 patients had missing data in stage and sub-classification Stage I: All of the following: Hemoglobin>10 g/dl,Serum calcium<10.5 mg/dL, normal bone structure,IgG<5 g/dL; IgA<3 g/dL, Urine light chain M-component<4 g/24h Stage II:Fitting neither Stage I nor Stage III Stage III: One or more of the following: Hemoglobin<8.5 g/dL, Serum calcium>12 mg/dL,Advanced lytic bone lesions,IgG>7 g/dL; IgA> 5 g/dL,Urine light chain M-component>12 g/24h Subclassification: A, serum creatinine<2.0 mg/dL;B, serum creatinine>2.0 mg/dL | Count of Participants | Participants |
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| ISS stage at diagnosis | ISS, International Staging System ISS stage I was defined as serum β2-microglobulin level less than 3.5 mg/L and serum albumin level ≥ 3.5 g/dL. ISS stage II included all patients with neither stage I nor stage III disease. ISS stage III was defined as serum β2-microglobulin level ≥ 5.5 mg/L, irrespective of serum albumin level | Count of Participants | Participants |
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| R-ISS stage at study entry | R-ISS, Revised International Staging System Stage I: Serum β2 microglobulin<3.5 mg/l; Serum albumin≥3.5 g/dl;Standard-risk chromosomal abnormalities (CA);Normal LDH Stage II: Not R-ISS stage I or III Stage III: Serum β2 microglobulin≥5.5 mg/L and either High-risk CA by FISH OR High LDH | Count of Participants | Participants |
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| Cytogenetic at study entry | Count of Participants | Participants |
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| Disease status with respect to last prior therapy | Total refractory MM included 2 categories of refractory:
| Count of Participants | Participants |
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| Best response to last prior anticancer therapy | Partial response (PR): had ≥50% reduction in serum M-protein and reduction of 24-hour urine M-protein by 90% or to <200 mg/24h Minimal response (MR): had ≥25% but ≤49% reduction of serum M-protein and reduction of 24h urine M-protein 50-89%. Progressive disease (PD): had a 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions Stable disease (SD): not meet the criteria for PR, MR or PD | Count of Participants | Participants |
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| Prior HSCT | HSCT, hematopoietic stem cell transplantation | Count of Participants | Participants |
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| Lines of prior chemotherapy | Count of Participants | Participants |
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| Weight | Median | Full Range | kg |
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| Height | Median | Full Range | cm |
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| Body surface area | Median | Full Range | m^2 |
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| Time from diagnosis to first plitidepsin infusion | Median | Full Range | months |
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| Time from last progressive disease to first infusion | Median | Full Range | weeks |
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| Lines of prior chemotherapy | Median | Full Range | Lines |
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| Agents of prior chemotherapy | Median | Full Range | Agents |
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| TTP to last anticancer therapy | Time to progression (TTP) was defined as the time, in months, from the date of the first infusion of last anticancer therapy to the date of documented PD previous study entry. | Median | Full Range | months |
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| 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 | Partial response (PR): ≥50% reduction in serum M-protein and reduction of 24-hour urine M-protein by 90% or to <200 mg/24h Minimal response (MR): ≥25% but ≤49% reduction of serum M-protein and reduction of 24h urine M-protein 50-89%. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions Stable disease (SD): not meet the criteria for PR, MR or PD Primary analysis should have been done once a total of 64 patients have received plitidepsin+BTZ+DXM with one futility analysis planned after the inclusion of 20 evaluable patients that had completed two full treatment cycles. Only 10 patients were treatedand 8 evaluable for the primary endpoint (ORR according to IMWG criteria). As a result of slow patient accrual, the study was closed before reaching the target enrollment | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Count of Participants | Participants | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
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| Primary | Overall Response Rate | The primary endpoint was overall response rate (ORR) (including stringent complete response [sCR], complete response [CR], very good partial response [VGPR] and partial response [PR]), according to the IMWG response criteria. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
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| Secondary | Clinical Benefit Rate | Clinical benefit rate defined as minimal response or better | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
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| Secondary | Disease Control Rate | Disease control rate defined as stable disease [SD] or better | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks |
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| Secondary | Duration of Response | Duration of Response defined as the time, in months, from the date of first documentation of response to the date of disease progression. Response was assessed according to the IMWG classification response criteria. | Only one patient achieved a partial response | Posted | Number | months | From the date of first documentation of response to the date of disease progression, up to 100 weeks |
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| Secondary | Time to Progression | Time to progression (TTP) was defined as the time, in months, from the date of the first infusion to the date of documented PD or death due to PD. TTP was to be censored on the date of the last tumor assessment or on the date of the first drug administration if there were no tumor assessments. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Median | 95% Confidence Interval | months | From the date of the first infusion to the date of documented PD or death due to PD, up to 100 weeks |
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| Secondary | Percentage of Participants With Progression Disease at 3 Months | Progression disease was defined as documented PD or death due to PD Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of the first infusion to the date of documented PD or death due to PD, up to 3 months |
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| Secondary | Percentage of Participants With Progression Disease at 6 Months | Progression disease was defined as documented PD or death due to PD. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of the first infusion to the date of documented PD or death due to PD, up to 6 months |
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| Secondary | Percentage of Participants With Progression Disease at 12 Months | Progression disease was defined as documented PD or death due to PD. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of the first infusion to the date of documented PD or death due to PD, up to 12 months |
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| Secondary | Progression-free Survival | Progression-free survival (PFS) was defined as the time, in months, from the date of first drug administration to the date of documented PD, or death (of any cause). If any patient was lost to follow-up before PD or received another antitumor therapy, PFS was to be censored on the date of the last tumor assessment. If there were no tumor assessments, these parameters were to be censored on the date of the first drug administration. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Median | 95% Confidence Interval | months | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 100 weeks |
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| Secondary | Percentage of Participants With Progression-free Survival at 3 Months | Progression-free Survival was defined as documented PD, or death of any cause. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 3 months |
|
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| Secondary | Percentage of Participants With Progression-free Survival at 6 Months | Progression-free Survival was defined as documented PD, or death of any cause. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Progression-free Survival at 12 Months | Progression-free survival (PFS) was defined as the time, in months, from the date of first drug administration to the date of documented PD, or death (of any cause). If any patient was lost to follow-up before PD or received another antitumor therapy, PFS was to be censored on the date of the last tumor assessment. If there were no tumor assessments, these parameters were to be censored on the date of the first drug administration Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of documented PD, or death (of any cause), up to 12 months |
| |||||||||||||||||||||||||||||||
| Secondary | Event-free Survival | Event-free survival (EFS) was defined as the time, in months, from the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death. The censoring rules defined above for PFS were used for EFS | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Median | 95% Confidence Interval | months | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 100 weeks |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Event-free Survival at 3 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. rogressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 3 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Event-free Survival at 6 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Event-free Survival at 12 Months | Event-free survival (EFS) was defined as the first drug-related event leading to treatment discontinuation, documented PD or death. Progressive disease (PD): 25% increase from the lowest response value in any of the following: serum M-protein, urine M-protein, BM plasma cell percentage, or difference in the kappa and lambda FLC. PD also diagnosed when an increase size or new bone lesions. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of onset of the first drug-related event leading to treatment discontinuation, documented PD or death, up to 12 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall survival (OS) was defined as the time, in months, from the date of first drug administration to the date of death (of any cause) or last patient contact (in this case, survival was to be censored on that date). | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Median | 95% Confidence Interval | months | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 100 weeks |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Overall Survival at 6 Months | Overall survival (OS) was defined as death of any cause. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 6 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Overall Survival at 12 Months | Overall survival (OS) was defined as death of any cause. | 1 died without any valid tumor assessment done 1 discontinued treatment-related AEs | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 12 months |
|
|
From first infusion to 30 days after the last administration of trial drug and until their resolution, an average of 2 years
Not provided
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 | Experimental | Plitidepsin was to be administered as a 3-hour (h) intravenous (i.v.) infusion at a dose of 5 mg/m2, on Day (D) 1 and 15, every four weeks (q4wk); BTZ was to be administered as a subcutaneous (s.c.) injection at a dose of 1.3 mg/m2 on D1, 4, 8 and 11, q4wk and DXM was to be taken orally at a dose of 40 mg/day on D1, 8, 15 and 22, q4wk. A cycle was defined as 28 days, plus any additional days required for dosing delays due to any reason. Treatment cycles were repeated q4wk. | 3 | 10 | 5 | 10 | 10 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haematoma | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Intramedullary rod insertion | Surgical and medical procedures | MedDRA (21.1) | Systematic Assessment |
| |
| Asthenia/Fatigue | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Extravasation | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Antithrombin III decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Blood cholesterol | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gastric disorder | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
On 29052018 the Sponsor closed the recruitment of the study due to the slow patient accrual. Besides the negative opinion of the EMA recommending the refusal of the marketing authorization for plitidepsin for MM reinforced the decision.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit. | Pharma Mar, S.A. | +34 918466000 | clinicaltrials@pharmamar.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 13, 2016 | Jul 24, 2020 | SAP_001.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 |
|---|---|
| C098980 | plitidepsin |
| D000069286 | Bortezomib |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
Not provided
Not provided
| Spain |
|
| PS 2 |
|
| Secretory Kappa light-chain disease |
|
| Secretory Lambda light-chain disease |
|
| IIIB |
|
| Missing |
|
| ISS III |
|
| Not done |
|
| Non available genetic results |
|
| Non available genetic results |
|
| SD |
|
| PD |
|
| No |
|
| 5 lines |
|
| 8 lines |
|
| 9 lines |
|
| PD |
|
|
|
|
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|
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| Units |
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| Counts |
|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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