A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma

NCT00229203 | Completed Phase 2 Results

• 1 other identifier: APL-B-014-03
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 hours intravenous infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM).

Conditions

Multiple Myeloma

Keywords

Myeloma; Aplidin; Plitidepsin; PharmaMar

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response

  Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: \>25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation. Treatmen failure: Reappearance of serum or urinary paraprotein

  Every 2 weeks until progression or death occurs.

Secondary Outcomes (3)

• Time to Progression (TTP)

  Every 2 weeks until progression or death due to progression occurs. Median TTP and TTP rates at 3 months and 6 months were assessed.

• Progression Free Survival (PFS)

  Every 2 weeks until progression or death occurs. Median PFS and PFS rates at 3 months and 6 months were assessed.

• Number of Patients With Overall Survival (OS)

  Start of treatment to death. At each patient visit while on treatment, then every 3m during follow-up. Median OS and OS rates at 6 months and 12 months were assessed.

Interventions

Plitidepsin DRUG

3-hour infusion every 2 weeks alone or in combination with dexamethasone

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient's legal representative if in accordance with local laws and regulations
• Age ≥ 18 years
• Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy ≥ 3 months.
• Patient was previously diagnosed with MM based on standard criteria and currently requires treatment because MM relapses following a response to standard chemotherapy or high-dose chemotherapy, or MM is refractory (i.e., failure to achieve at least complete response (CR), partial response (PR) or stable disease (SD)) to their most recent chemotherapy.
• Patient has measurable disease, defined as follows:
• For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.
• For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. Magnetic resonance imaging (MRI), Computerized Axial Tomography (CT-Scan)).
• Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade \< 2 sensitive peripheral neuropathy is allowed.
• Patient has the following laboratory values within 14 days before day 1, cycle 1:
• Platelet count ≥ 50 x109/L, hemoglobin ≥ 8.0 g/dl and absolute neutrophil count (ANC) ≥ 1.0x109/L; lower values may be accepted if clearly are due to bone marrow involvement by multiple myeloma.
• Corrected serum calcium \< 14mg/dL.
• Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
• Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.
• Total bilirubin: ≤ 1.5 x the upper limit of normal.

You may not qualify if:

• Prior therapy with Aplidin®.
• Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)
• History of another neoplastic disease. The exceptions are:
• non-melanoma skin cancer,
• carcinoma in situ of uterine cervix,
• any other cancer curatively treated and no evidence of disease for at least 10 years.
• Other relevant diseases or adverse clinical conditions:
• History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.
• Previous mediastinal radiotherapy.
• Uncontrolled arterial hypertension despite optimal medical therapy.
• Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².
• Symptomatic arrhythmia or any arrhythmia requiring treatment.
• History of significant neurological or psychiatric disorders
• Active infection
• Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (1)

Jerome Lipper Multiple Myeloma Center - Dept of Medical Oncology - Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

plitidepsin

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

32 patients were treated with plitidepsin as single agent;afterwards 19 of them were treated with plitidepsin+dexamethasone combination.Therefore 32+19=51 is the no. patients at risk for plitidepsin and 19 is no. of patients at risk for dexamethasone

Results Point of Contact

• Title: Claudia Silvia Corrado M.D.
• Organization: PharmaMar USA Inc

cscorrado@pharmamar.com

1 212 201 6770

Study Officials

• Paul Richardson, MD

  Chief division hematological malignancies - Medical Oncology - Dana Farber Cancer Institute - Harvard Medical School, Boston

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 27, 2005
• First Posted: September 29, 2005
• Study Start: February 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: December 24, 2009
• Results First Posted: December 14, 2009

Record last verified: 2009-12

Locations

US (1)