Efficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients

Nordic Myeloma Study Group

Status and phase

Completed

Phase 3

Conditions

Multiple Myeloma

Treatments

Drug: bortezomib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00417911

NMSG 15/05

EudraCT No: 2005-002756-18

Details and patient eligibility

About

Multiple myeloma is a malignant incurable hematological disease where survival has been significantly improved by high-dose melphalan with autologous stem cell support (ASCT) in younger patients. However, the disease will eventually relapse and new treatment is demanded. Bortezomib is a newly approved drug for treating relapsing multiple myeloma. It has a different biological effect and response even in patients refractory to conventional chemotherapy. The purpose of the study is in a randomized design to investigate if addition of bortezomib by 20 injections during a 4 months period starting 3 month after ASCT can prolong the time to progression compared to patients receiving no consolidation or maintenance therapy.

Full description

Rationale:

ASCT prolongs EFS and OS for myeloma patients < 65 years of age. During the period from ASCT to progression most myeloma patients experience few symptoms and have a good quality of life11. A further prolongation of EFS would be a big step forward in myeloma treatment. Bortezomib is a new promising agent, which has shown clear anti-myeloma effect in heavily pre-treated patients. After ASCT the tumour cell burden is low and it is the hypothesis of this clinical trial that the unique mechanism of action of bortezomib may reduce the number of tumour cells even further and by doing so prolong EFS.

Primary objective:

* Evaluate the effect on EFS (an event is defined as either progression or death of any cause without preceding progression) of consolidation treatment with bortezomib after ASCT compared to no consolidation

Secondary objectives:

Overall survival from ASCT
Overall survival from start of relapse treatment
Time to need for relapse treatment
Response rate in patients not in CR following ASCT
Toxicity from consolidation treatment
Quality of life
Cost utility
Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments

Enrollment

400 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Symptomatic myeloma diagnosis according to criteria in attachment 3
ASCT is performed or has been performed in the last five weeks (time limit two weeks for patients randomised at 2nd transplantation) as a part of primary therapy
Signed informed consent given prior to any study related activities have been performed

Exclusion criteria

Prior exposure to bortezomib
Allogeneic transplantation scheduled as a part of the primary treatment
Neuropathy > Grade 2 (neurological symptoms interfering with ADL)
Non-secreting myeloma
Other concurrent disease making bortezomib treatment unsuitable
Positive pregnancy test (only applicable for women with childbearing potential)
Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 6, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
History of hypotension or has decreased blood pressure (sitting systolic blood pressure [SBP] £100 mmHg and/or sitting diastolic blood pressure [DBP] £60 mmHg)
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Have received an experimental drug or used an experimental medical device within 4 weeks prior to inclusion into the study