Multiple MyelomaPhase 2NCT03117361
Trial of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Bortezomib and Lenalidomide
A Phase 2 study testing plitidepsin, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by PharmaMar at 13 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- plitidepsin, Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 8 May 2017to 30 Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Serum M-protein ≥ 0.5 g/dL or ≥ 0.2 g/24-h urine light chain (UFLC) excretion.
- In patients who lack measureable M-protein in serum or urine, i.e., serum M-protein < 0.5 g/dL and urine M-protein < 0.2 g/24 h, serum free light chain (SFLC) levels are most informative. SFLC levels can be used only if the baseline SFLC ratio is abnormal (<0.26 or >1.65), indicating clonality. In addition, the baseline SFLC level must be ≥10 mg/dl of the appropriate involved light chain isotype.
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- When applicable, measurable soft tissue plasmacytoma ≥ 2 cm, by either physical examination and/or applicable radiological evaluation (i.e., magnetic resonance imaging [MRI], computed tomography [CT]-scan).
- 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:
- Hemoglobin ≥ 8 g/dL.
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (≥ 0.5 x 109/L if due to extensive bone marrow [BM] involvement by ≥ 50% of plasma cells in BM biopsy). Screening of ANC should be independent of granulocyte- and granulocyte/macrophage-colony stimulating factor (G-CSF and GM-CSF) support for at least one week and of pegylated G-CSF for at least two weeks.
- Platelet count ≥ 50,000/mm3 (50.0 x 109/L) for patients in whom < 50% of the BM nucleated cells are plasma cells.
- Platelet count ≥ 25,000/mm3 (25.0 x 109/L) for patients in whom ≥ 50% of BM nucleated cells are plasma cells.
- Serum total bilirubin < 1.5 x institutional upper limit of normal (ULN) (except when Gilbert syndrome is clearly documented and other liver function tests are within normal levels).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x institutional ULN and alkaline phosphatase (AP) ≤ 2.5 x institutional ULN.
- Creatinine clearance (CrCl) > 30 mL/min, measured or calculated according to Cockcroft and Gault's formula.
- Albumin ≥ 2.5 g/dl.
- 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.
Who cannot join
- 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:
- Uncontrolled psychiatric illness or medical illness that the Investigator feels will compromise the patient's tolerance of the trial medication.
- Significant non-neoplastic liver disease.
- Uncontrolled endocrine diseases (i.e., requiring relevant changes in medication within the last month, or hospital admission within the last three months).
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- Uncontrolled systemic infection.
- Acute infiltrative pulmonary and pericardial disease.
- Other relevant cardiac conditions:
- Symptomatic arrhythmia (excluding anemia-related grade ≤ 2 sinusal tachycardia) or any arrhythmia requiring ongoing treatment, and/or prolonged grade ≥ 2 QT-QTc; or presence of unstable atrial fibrillation (according to the National Cancer Institute Common Terminology Criteria for the Classification of Adverse Events [NCI-CTCAE] v4.0). Patients on treatment for stable atrial fibrillation are allowed, provided they do not meet any other cardiac or prohibited drug exclusion criterion.
- History or presence of unstable angina, myocardial infarction, valvular heart disease, cardiac amyloidosis or congestive heart failure within the last 12 months.
- Uncontrolled arterial hypertension (≥ 150/100 mmHg) despite optimal medical therapy.
- Previous treatment with doxorubicin at cumulative doses of > 400 mg/m², or equivalent.
- 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:
- Nitrosoureas must be discontinued six weeks prior to Cycle (C) 1, D1.
- Thirty days for other CTs and 15 days for other biological agents prior to C1 D1.
- Thirty days after the end of any prior radiation or radionuclide therapy (six weeks in the case of prior extensive external beam radiation, with more than 25% of BM distribution).
- 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.
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
Spain8 sites
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916
Institut Català d´Oncologia Girona
Girona, 17007
Institut Català d´Oncologia L´Hospitalet
L'Hospitalet de Llobregat, 08908
Hospital General Universitario J.M. Morales Meseguer
Murcia, 30008
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Hospital Universitario de Salamanca
Salamanca, 37007
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706
Complejo Hospitalario Regional Virgen Del Rocio
Seville, 41013
Italy3 sites
Policlinico Vittorio Emanuele Hospital
Catania, 95123
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, 00126
France2 sites
CHRU de Lille - Hôpital Claude Huriez
Lille, 59037
Institut Gustave Roussy
Villejuif, 94800
About this study
Official title: Phase II Trial of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Multiple Myeloma Patients 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 Multiple Myeloma (MM) double refractory to bortezomib and lenalidomide.
Read the detailed description
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.
- Conditions
- Multiple Myeloma
- Being tested
- plitidepsin, Bortezomib, Dexamethasone
- Keywords
- multiple myeloma, plitidepsin, Aplidin
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plitidepsinDrug
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.
BortezomibDrug
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
DexamethasoneDrug
DXM orally at a dose of 40 mg/day on Days 1, 8, 15 and 22 every four weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: plitidepsin; Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
Secondary outcomes (18)
Clinical Benefit Rate
Clinical benefit rate defined as minimal response or better
Measured: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
Disease Control Rate
Disease control rate defined as stable disease [SD] or better
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2017
- Study start8 May 2017
- Primary completion30 Jul 2018
- Study completion30 Jul 2018
Why it stopped: PharmaMar has decided to end this study due to the slow recruitment rate of the trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03117361
- Sponsor's protocol ID
- APL-B-022-15
- Status last verified
- Nov 2020
- First submitted
- 12 Apr 2017
- Last updated
- 2 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Multiple Myeloma Patients Double Refractory to Bortezomib and Lenalidomide
- ClinicalTrials.gov ID
- NCT03117361
- Acronym / sponsor ID
- APL-B-022-15
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, plitidepsin, Aplidin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PharmaMar has decided to end this study due to the slow recruitment rate of the trial
- Enrolment
- 10 participants (actual)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- 8 May 2017 (actual)
- Primary completion
- 30 Jul 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 17 Apr 2017 (actual)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: plitidepsin, Drug: Bortezomib, Drug: DexamethasonePlitidepsin + 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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).
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| plitidepsinPatients received plitidepsin as a 3-hour i.v. infusion at a dose of 5 mg/m2 on Days 1 and 15 every Four Weeks. | Drug | Experimental |
| BortezomibBTZ 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 | Drug | Experimental |
| DexamethasoneDXM orally at a dose of 40 mg/day on Days 1, 8, 15 and 22 every four weeks | Drug | Experimental |
Primary outcome
Overall Response
Time frame: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
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
Overall Response Rate
Time frame: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
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.
18 secondary outcomes
Clinical Benefit Rate
Time frame: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
Disease Control Rate
Time frame: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks
Duration of Response
Time frame: From the date of first documentation of response to the date of disease progression, up to 100 weeks
Time to Progression
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From the date of first drug administration to the date of death (of any cause) or last patient contact, up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing plitidepsin, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by PharmaMar at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, Italy, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response (time frame: From the date of first drug administration to the date of at least one disease assessment, up to 100 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2020.