Pomalidomide, Cyclophosphamide and Prednisone (PCP) in Patients With Multiple Myeloma (MM) Relapsed and/or Refractory to Lenalidomide

This is a prospective multicenter phase I followed by a phase II trial designed to evaluate the safety and efficacy of the combination of Pomalidomide with Cyclophosphamide and Prednisone in patients with multiple myeloma relapsed and/or refractory to lenalidomide.

Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).

The pre-treatment period includes: screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the evaluation of inclusion criteria described above. Subjects who meet all the inclusion criteria will be enrolled.

The treatment period includes: administration of the salvage treatment PCP for 6 cycles and maintenance treatment. In order to assess the toxicity of treatment, patients will attend study centre visits at least every 2 weeks, unless clinically indicated. The response will be assessed after each cycle.

During the LTFU period, after development of confirmed PD, all patients are to be followed for survival every 1-3 months via telephone or office visit.

Inclusion criteria

• Age ≥ 18 years.
• Patient with multiple myeloma who received 1 to 3 lines of treatment (including high-dose chemotherapy with stem cell support, conventional poli-chemotherapy, thalidomide- , bortezomib- and melphalan-based regimens) and is relapsed or relapsed and refractory (that means relapsed while on salvage or progression within 60 days of most recent therapy) to lenalidomide therapy.
• Patient has clinical relapse of MM based on standard criteria.
• Patient has measurable disease, defined as follows:

• For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value (greater than 1 g/dL of IgG M-protein, greater than 0.5 g/dL of IgA M-protein or IgD M-protein OR urine light-chain excretion of more than 200 mg/24 hours)
• For oligo- or non-secretory multiple myeloma, measurable disease is defined by the presence of measurable soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e., MRI, CT scan).

A measurable lesion is defined as a lesion with minimum largest diameter of >20 mm (if measured by conventional techniques such as physical exam, conventional CT scan, MRI) or of >10 mm (if measured by spiral CT scan) in one dimension.

• Patient has a Karnofsky performance status ≥ 60%.

Exclusion criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other concomitant standard/experimental anti-myeloma drug or therapy.
• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis Other malignancy within the past 5 years. Exceptions: basal cell or non metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1 carcinoma of the cervix.
• Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pulmonary disease, cardiac disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.