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

NCT02100657 | Completed Phase 1 Results

• 1 other identifier: APL-A-012-13
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; plitidepsin; APLIDIN

Outcome Measures

Primary Outcomes (4)

• 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.

  After 28-day cycle

• 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.

  After 28-day cycle

• 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.

  After 28-day cycle

• 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

  After 28-day cycle

Secondary Outcomes (9)

• Response According to International Myeloma Working Group Criteria

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

• Overall Response Rate

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

• Duration of Response

  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

  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

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

Study Arms (1)

plitidepsin + bortezomib + dexamethasone

EXPERIMENTAL

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: Plitidepsin; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Plitidepsin DRUG

plitidepsin + bortezomib + dexamethasone

Bortezomib DRUG

plitidepsin + bortezomib + dexamethasone

Dexamethasone DRUG

plitidepsin + bortezomib + dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Plasma cell leukemia at the time of study entry
• Contraindication for the use of steroids

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (7)

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Universitario Germans Trias I Pujol

Badalona, Barcelona, 08916, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitari i Politècnic la Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

plitidepsin; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Pharma Mar S.A.
• Organization: Pharma Mar S.A.

clinicaltrials@pharmamar.com

00 34 91846 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: April 1, 2014
• Study Start: June 1, 2014
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: October 12, 2020
• Results First Posted: October 12, 2020

Record last verified: 2020-09

Locations

ES (6); FR (1)