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Multiple MyelomaPhase 1NCT02100657

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

A Phase 1 study testing Plitidepsin, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by PharmaMar at 7 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. 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
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
7 sitesin 2 countries
Study dates
Jun 2014to Jun 2018
Phase
Phase 1
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

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

Spain6 sites

  • Hospital Universitario Germans Trias I Pujol

    Badalona, Barcelona, 08916

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

  • Clínica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Salamanca

    Salamanca, 37007

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Universitari i Politècnic la Fe

    Valencia, 46026

Other trials in Spain

France1 site

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: 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.

Read the 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.

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.

Study groups in NCT02100657
Study groupRoleWhat they receive
plitidepsin + bortezomib + dexamethasoneExperimentalPlitidepsin 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
Receives: Drug: Plitidepsin; Drug: Bortezomib; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone

    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.

    Measured: After 28-day cycle

  2. Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone

    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.

    Measured: After 28-day cycle

  3. Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib

    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.

    Measured: After 28-day cycle

  4. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    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

    Measured: After 28-day cycle

Secondary outcomes (9)

  1. Response According to International Myeloma Working Group Criteria

    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

    Measured: Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years

  2. Overall Response Rate

    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

    Measured: Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years

  3. Duration of Response

    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

    Measured: From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years

  4. Time to Progression

    Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.

    Measured: From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years

  5. Time to Progression Rates

    Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.

    Measured: From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years

  6. Progression-free Survival

    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

    Measured: from the date of the first infusion to the date of documented PD or death, up to 4 years

  7. Progression-free Survival Rates

    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

    Measured: From the date of the first infusion to the date of documented PD or death, up to 4 years

  8. Event-free Survival

    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

    Measured: From the date of first infusion to the date of documented PD or death, up to 4 years

  9. Event-free Survival Rates

    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

    Measured: from the date of first infusion to the date of documented PD or death, up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionJun 2018
  4. Study completionJun 2018

Resources

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 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02100657
Sponsor's protocol ID
APL-A-012-13
Status last verified
Sep 2020
First submitted
21 Mar 2014
Last updated
12 Oct 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Plitidepsin, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by PharmaMar at 7 sites in 2 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 3 inclusion and 11 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: finished, as of the sponsor's last update on 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Spain, 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 12 Oct 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?

Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone (time frame: After 28-day cycle). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02100657.

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 12 Oct 2020.

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