"Phase II Multicenter, Open-Label, Clinical and Pharmacokinetic Study of Aplidin® As A 3-Hour Infusion Every 2 Weeks Alone or in Combination With Dexamethasone, in Pre-Treated Patients With Relapsing or Refractory Multiple Myeloma."
1. 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
2. Age ≥ 18 years
3. Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
4. Life expectancy ≥ 3 months.
5. 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
6. 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)).
7. 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.
8. 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.
- Calculated Creatinine clearance: ≥ 40 mL/minute (by means of Crockoft and
9. Left ventricular ejection fraction within normal limits.
1. Prior therapy with Aplidin®.
2. Pregnant or lactating women; men and women of reproductive potential who are not
using effective contraceptive methods (double barrier method, intrauterine device,
3. 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
4. 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.
- Myopathy or any clinical situation that causes significant and persistent
elevation of creatine kinase (CK)(>2.5 ULN in two different determinations
performed with one week apart)
- Significant non-neoplastic liver disease (e.g. cirrhosis, active chronic
- Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or
hyperthyroidism) (i.e. requiring relevant changes in medication within the last
month, or hospital admission within the last 3 months)
5. Limitation of the patient's ability to comply with the treatment or follow-up
6. Treatment with any investigational product in the 30 days period before inclusion in
the study or radiotherapy in the 4 weeks before inclusion in the study. Other
previous treatments should have been completed 3 weeks before inclusion in the study,
and in case of high dose chemotherapy, 8 weeks.
7. Known hypersensitivity to Aplidin®, mannitol, cremophor, or ethanol or dexamethasone.