Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Multiple Myeloma

September 17, 2020 updated by: PharmaMar

Phase I Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Study of Plitidepsin (Aplidin®) to determine the recommended dose (RD) of plitidepsin in Combination with Bortezomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Trial of Plitidepsin (Aplidin®) to determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM), to determine the efficacy of the combination plitidepsin/bortezomib/dexamethasone, to evaluate the safety and tolerability of the combination in patients with relapsing and/or refractory MM and to study the pharmacokinetics (PK) and pharmacodynamics (PDy) of plitidepsin in combination with bortezomib and dexamethasone.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Spain
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center Madrid
      • Salamanca, Spain, 37007
        • Hospital Universitario Salamanca
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Hospital Universitari i Politècnic La Fe
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitario Germans Trias i Pujol
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years.
  • Prior autologous transplantation (HSCT) patients are allowed.
  • Patients must have received at least one previous treatment line of induction, chemotherapy, chemotherapy and transplantation or previous treatment with bortezomib or another proteasome drug

Exclusion Criteria:

  • Previous treatment with plitidepsin.
  • Active or metastatic primary malignancy other than MM.
  • Serious concomitant systemic disorders
  • History of hypersensitivity reactions to bortezomib, polyoxyl 35 castor oil or mannitol
  • Neuropathy
  • Pregnant and/or lactating women
  • HIV infection
  • Active hepatitis B or C virus infection.
  • Treatment with any Investigational Medicinal Product (IMP) in the 30 days before inclusion in the study
  • Plasma cell leukemia at the time of study entry
  • Contraindication for the use of steroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: plitidepsin + bortezomib + dexamethasone

Plitidepsin will be administered as a 3-hour (h) intravenous (i.v.) infusion on Day (D) 1 and 15, every four weeks (q4wk).

Bortezomib will be administered as a subcutaneous (s.c.) injection on D1, 4, 8 and 11, q4wk, for a maximum of eight cycles.

Dexamethasone will be taken orally on D1, 8, 15 and 22, q4wk
Drug: Dexamethasone
Drug: Bortezomib
Drug: Plitidepsin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone
Time Frame: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
After 28-day cycle
Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone
Time Frame: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
After 28-day cycle
Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib
Time Frame: After 28-day cycle
To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
After 28-day cycle
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: After 28-day cycle

DLTs were defined as:

Hematological Toxicity

  • Grade 3/4 neutropenia associated with fever or lasting>7 days related to the study treatment
  • Grade 3/4 thrombocytopenia accompanied by grade 3/4 hemorrhage
  • Extensive bone marrow (BM) infiltration, DLT was defined as grade 4 thrombocytopenia with grade 3/4 hemorrhage or grade 4 neutropenia lasting >7 days or with fever Non-hematological Toxicity
  • Grade 3/4 nausea and vomiting refractory to antiemetic therapy
  • Grade≥3 muscular Adverse events (AE) (myalgia, muscular weakness, muscle cramps, myopathy)
  • Grade≥3 alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) lasting more than 1 week
  • Grade≥3 bilirubin increase
  • Grade≥3 creatine phosphokinase (CPK) increase

  • Cardiac toxicity

    • Symptomatic or treatment-requiring grade ≥1 cardiac arrhythmia related to plitidepsin
    • Grade≥1 left ventricular systolic dysfunction related to plitidepsin
  • Neuropathic pain and peripheral sensory neuropathy related to BTZ
After 28-day cycle

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response According to International Myeloma Working Group Criteria
Time Frame: Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Stringent complete response (sCR) normal Free Light Chains (FLC) ratio. No clonal cells Complete response (CR) no serum/urine M-protein, no evidence of soft tissue plasmacytoma. <5% clonal plasma cells Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) ≥50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas Minor response (MR) 25%-49% reduction of serum M-protein and 50-89% reduction of 24h urine M-protein. 25-49% reduction in size of soft tissue plasmacytomas. No increase in size or number of bone lesions Stable disease (SD) No sCR, CR, VGPR, PR, MR or PD Progressive disease (PD) 25% increase from the lowest value: serum M-protein, urine M-protein, BM plasma cell. Increase in size, new bone lesions, soft tissue plasmacytomas or serum calcium >11.5 mg/dL
Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Overall Response Rate
Time Frame: Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Overall response rate (ORR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR) according to the International Myeloma Working Group (IMWG) criteria
Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Duration of Response
Time Frame: From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years
Duration of response (DR) was analyzed for all patients in whom a response had been observed and was calculated from the date of the first documentation of response to the date of PD or further therapy or death
From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years
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 4 years
Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
Time to Progression Rates
Time Frame: From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
Progression-free Survival
Time Frame: from the date of the first infusion to the date of documented PD or death, up to 4 years
Progression-free survival (PFS) was calculated from the date of the first infusion to the date of documented PD or death (regardless of the reason), whichever comes first
from the date of the first infusion to the date of documented PD or death, up to 4 years
Progression-free Survival Rates
Time Frame: From the date of the first infusion to the date of documented PD or death, up to 4 years
Progression-free survival (PFS) was calculated from the date of the first infusion to the date of documented PD or death (regardless of the reason), whichever comes first
From the date of the first infusion to the date of documented PD or death, up to 4 years
Event-free Survival
Time Frame: From the date of first infusion to the date of documented PD or death, up to 4 years
Event-free survival (EFS) was calculated from the date of first infusion to the date of documented PD or death, but could include additional events besides death and PD that were considered of importance
From the date of first infusion to the date of documented PD or death, up to 4 years
Event-free Survival Rates
Time Frame: from the date of first infusion to the date of documented PD or death, up to 4 years
Event-free survival (EFS) was calculated from the date of first infusion to the date of documented PD or death, but could include additional events besides death and PD that were considered of importance
from the date of first infusion to the date of documented PD or death, up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PharmaMar

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 21, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APL-A-012-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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