Phase II Study to Assess the Safety, Efficacy and Tolerability of Combination Therapy With Bortezomib, Doxorubicin and Dexamethasone (PAD) as Therapy for Patients With Relapsed or Refractory Myeloma.
Inclusion Criteria:
- Patients aged at least 18 years with MM requiring therapy for relapsed or refractory
disease.
- Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup
allocation is shown in 4.1
- Measurable serum and/or urine paraprotein, or serum free light chain
- Performance Status (PS) 0-3
- Serum bilirubin values <1.5 times the upper limit of normal
- Serum ALT/AST values <2.5 times the upper limit of normal
- Able to give informed consent
Exclusion Criteria:
- Females of child-bearing potential without a negative pregnancy test, immediately
prior to the start of PAD therapy and/or unwilling to use barrier contraceptive
precautions throughout the study or who are pregnant or breast-feeding
- Men with partners of child bearing potential unwilling to use a medically acceptable
form of contraception
- Patients with non-secretory MM and no measurable elevation of serum free light chain
- Performance status 4 (ECOG)
- Patient has a platelet count <75 x 109/L within 14 days before enrolment
- Patient has an absolute neutrophil count <1.0 x 109/L within 14 days before enrolment
- Patient has a serum creatinine > 400 mol/l at the time of enrolment
- Patient has Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI
Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) within 14 days
before enrolment
- Cardiac ejection fraction <40% by echocardiography or MUGA scan
- Known HIV seropositivity (obligatory testing is not necessary)
- Known Hepatitis B or C (obligatory testing is not necessary)
- Patients who have received more than one autologous transplant
- Use of any investigational drug within 4 weeks prior to enrolment or any patients
scheduled to receive any investigational drug during the course of the study
- Previous Bortezomib therapy
- Patients who have a medical or psychiatric condition which, in the opinion of the
investigator, contraindicates the patient's participation in this study
- Previous or concurrent malignancies at other sites, with the exception of
appropriately treated localized epithelial skin or cervical cancer. Patients with
remote histories (>5 years) of other cured tumours may be entered
- Plasma exchange within 21 days of enrolment