- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02100657
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
39
Phase
- 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
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Villejuif, France, 94805
- Institut Gustave Roussy
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Madrid, Spain, 28033
- MD Anderson Cancer Center Madrid
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Salamanca, Spain, 37007
- Hospital Universitario Salamanca
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Sevilla, Spain, 41013
- Hospital Universitario Virgen del Rocio
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Valencia, Spain, 46026
- Hospital Universitari i Politecnic La Fe
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Barcelona
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Badalona, Barcelona, Spain, 08916
- Hospital Universitario Germans Trias i Pujol
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Navarra
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Pamplona, Navarra, Spain, 31008
- Clinica Universidad de Navarra
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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
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 |
Intervention / Treatment |
---|---|
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone
Time Frame: After 28-day cycle
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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.
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After 28-day cycle
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Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone
Time Frame: After 28-day cycle
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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.
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After 28-day cycle
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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.
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After 28-day cycle
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Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: After 28-day cycle
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DLTs were defined as: Hematological Toxicity
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After 28-day cycle
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Secondary Outcome Measures
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
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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
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Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
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Overall Response Rate
Time Frame: Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
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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
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Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
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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
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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
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From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years
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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
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Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
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From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
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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
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Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
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From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
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Progression-free Survival
Time Frame: from the date of the first infusion to the date of documented PD or death, up to 4 years
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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
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from the date of the first infusion to the date of documented PD or death, up to 4 years
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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
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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
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From the date of the first infusion to the date of documented PD or death, up to 4 years
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Event-free Survival
Time Frame: From the date of first infusion to the date of documented PD or death, up to 4 years
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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
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From the date of first infusion to the date of documented PD or death, up to 4 years
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Event-free Survival Rates
Time Frame: from the date of first infusion to the date of documented PD or death, up to 4 years
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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
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from the date of first infusion to the date of documented PD or death, up to 4 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
June 1, 2014
Primary Completion (ACTUAL)
June 1, 2018
Study Completion (ACTUAL)
June 1, 2018
Study Registration Dates
First Submitted
March 21, 2014
First Submitted That Met QC Criteria
March 27, 2014
First Posted (ESTIMATE)
April 1, 2014
Study Record Updates
Last Update Posted (ACTUAL)
October 12, 2020
Last Update Submitted That Met QC Criteria
September 17, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
- Bortezomib
Other Study ID 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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