Myeloma X Relapse (Intensive)

Trial overview

A phase III study to determine the role of a second autologous stem cell transplant as consolidation therapy in patients with relapsed multiple myeloma following prior high-dose chemotherapy and autologous stem cell rescue.

Inclusion criteria

1. Diagnosed with symptomatic (including non-secretory) multiple myeloma previously treated with standard chemotherapy and autologous transplantation.
2. Requiring therapy for first Progressive Disease (PD) (where PD is determined according to the International uniform response criteria for myeloma. Patients previously immunofixation negative who are now immunofixation positive need to demonstrate a greater than 5g/liter absolute increase in paraprotein).
3. Demonstrate PD requiring treatment at least 18 months from time of first transplant.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
5. Aged at least 18 years.
6. Adequate full blood count within 14 days before registration:
a. Platelet count ≥50x109/L
b. Absolute neutrophil count (ANC) 1x109/L
7. Adequate renal function within 14 days before registration:
a. Creatinine clearance ≥30ml/min
8. Adequate hepatobiliary function within 14 days before registration:
a. Total bilirubin <2 x upper limit of normal (ULN)
b. ALT/AST <2.5 x ULN
9. Adequate pulmonary function within 14 days before registration:
a. No evidence of a history of pulmonary disease. If a history, then KCO/DLCO (Carbon Monoxide diffusion in the lung) ≥50% and/or no requirement for supplementary continuous O2
10. Adequate cardiac function within 14 days before registration:
a. Left ventricular ejection fraction (LVEF) ≥40%.
11. If female and of childbearing potential, must have a negative pregnancy test (either serum or urine hCG) within 24 hours prior to start of PAD therapy.
12. Provided written informed consent.

Exclusion criteria

1. Received therapy for their relapsed disease other than local radiotherapy, therapeutic plasma exchange, or dexamethasone up to a maximum of 200mg. (Radiotherapy since pervious transplant sufficient to alleviate or control pain of local invasion is permitted. Patients who have received hemi-body radiation or similar since previous transplant will not be eligible).
2. ECOG Performance Status 3-4.
3. .≥Grade 2 peripheral neuropathy within 14 days before registration.
4. Known HIV or Hepatitis B/C seropositivity (testing is not required for the trial).
5. Use of any investigational drug within 4 weeks prior to registration, or scheduled to
receive any investigational drug during the course of the study.
6. Known resistance to combined bortezomib, doxorubicin and dexamethasone (PAD) therapy.
7. Known history of allergy contributable to compounds containing boron or mannitol.
8. Any medical or psychiatric condition which, in the opinion of the investigator,
contraindicates the patient’s participation in this study.
9. Previous or concurrent malignancies at other sites, with the exception of appropriately
treated localised epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumours may be entered.
10. Pregnant or breast feeding.
11. Unwilling to use adequate contraception during the study and for 6 months after the end of the study treatment if female of childbearing potential, or male whose partner is a female of childbearing potential unless they are surgically sterile.