High-Dose Melphalan and a Second Stem Cell Transplant or Low-Dose Cyclophosphamide in Treating Patients With Relapsed Multiple Myeloma After Chemotherapy
- Conditions
- Multiple Myeloma and Plasma Cell Neoplasm
- Interventions
- Registration Number
- NCT00747877
- Lead Sponsor
- Leeds Cancer Centre at St. James's University Hospital
- Brief Summary
RATIONALE: Giving chemotherapy and bortezomib before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and bortezomib. It is not yet known whether high-dose melphalan given together with a second stem cell transplant is more effective than low-dose cyclophosphamide in treating patients with relapsed multiple myeloma.
PURPOSE: This randomized phase III trial is studying giving high-dose melphalan together with a second stem cell transplant to see how well it works compared with low-dose cyclophosphamide in treating patients with relapsed multiple myeloma after chemotherapy.
- Detailed Description
OBJECTIVES:
Primary
* To determine the effect on freedom from disease progression in patients with relapsed multiple myeloma treated with re-induction therapy comprising bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) followed by a second autologous stem cell transplantation (ASCT) with high-dose melphalan vs low-dose cyclophosphamide consolidation therapy.
Secondary
* To assess the response rate of PAD in patients following a previous autograft.
* To compare the overall response rate of patients following high-dose melphalan chemotherapy and autologous stem cell transplantation with low-dose cyclophosphamide consolidation therapy.
* To assess the overall survival of patients treated with this regimen.
* To assess the safety and toxicity of a second ASCT in these patients.
* To assess the safety and toxicity of PAD in these patients.
* To assess the feasibility of stem cell collection following PAD in these patients.
* To determine the impact of this regimen on pain and quality of life in these patients.
OUTLINE: This is a multicenter study.
* Re-induction (PAD) therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11, doxorubicin hydrochloride IV continuously on days 1-4, and oral dexamethasone on days 1-4 (and days 8-11 and 15-18 of course 1 only). Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
* Peripheral blood stem cell (PBSC) mobilization and harvest: Within 6-12 weeks, some patients receive cyclophosphamide IV on day 0 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 1 and continuing to time of PBSC harvest. PBSCs are then collected.
Patients who successfully complete re-induction therapy and have adequate PBSC mobilization are stratified according to length of first remission or plateau (≤ vs ≥ 24 months) and response to PAD re-induction therapy (stable disease vs ≥ partial response). Patients are randomized to 1 of 2 arms.
* Arm I (high-dose melphalan consolidation therapy): Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.
* Arm II (low-dose cyclophosphamide consolidation therapy): Patients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.
Patients complete the EORTC QLQ-C30 and EORTC QLQ-MY20, the Brief Pain Inventory Short Form (BPI-SF), and the Leeds Assessment of Neuropathic Symptoms and Signs (Self Assessment) Pain Scale (S-LANSS) questionnaires at baseline and after completion of re-induction therapy.
Patients are followed monthly for up to 100 days after ASCT or at 30 days after low-dose cyclophosphamide and then every 3 months for 5 years.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 460
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Arm I autologous hematopoietic stem cell transplantation Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0. Arm I melphalan Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0. Arm II cyclophosphamide Patients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.
- Primary Outcome Measures
Name Time Method Time to disease progression
- Secondary Outcome Measures
Name Time Method Response rate to bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) Overall response rate following randomized treatments Overall survival Progression-free survival Toxicity and safety of autologous stem cell transplantation Toxicity and safety of weekly cyclophosphamide Toxicity and safety of PAD therapy Feasibility of stem cell collection Pain Quality of life
Trial Locations
- Locations (53)
Raigmore Hospital
🇬🇧Inverness, Scotland, United Kingdom
Ysbyty Gwynedd
🇬🇧Bangor, Wales, United Kingdom
Glan Clwyd Hospital
🇬🇧Rhyl, Denbighshire, Wales, United Kingdom
Singleton Hospital
🇬🇧Swansea, Wales, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, England, United Kingdom
Birmingham Heartlands Hospital
🇬🇧Birmingham, England, United Kingdom
Basingstoke and North Hampshire NHS Foundation Trust
🇬🇧Basingstoke, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Saint Richards Hospital
🇬🇧Chichester, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
St. George's Hospital
🇬🇧London, England, United Kingdom
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom
University College of London Hospitals
🇬🇧London, England, United Kingdom
James Cook University Hospital
🇬🇧Middlesbrough, England, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, England, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, England, United Kingdom
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Arrowe Park Hospital
🇬🇧Wirral, England, United Kingdom
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
🇬🇧Birmingham, England, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, England, United Kingdom
Pinderfields General Hospital
🇬🇧Wakefield, Scotland, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧Norwich, England, United Kingdom
Oxford Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, England, United Kingdom
King's College Hospital
🇬🇧London, England, United Kingdom
Frenchay Hospital
🇬🇧Bristol, England, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
St. Helier Hospital
🇬🇧Carshalton, England, United Kingdom
Torbay Hospital
🇬🇧Torquay, England, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, England, United Kingdom
Dorset County Hospital
🇬🇧Dorchester, England, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, England, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, England, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Christie Hospital
🇬🇧Manchester, England, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, England, United Kingdom
Gloucestershire Oncology Centre at Cheltenham General Hospital
🇬🇧Cheltenham, England, United Kingdom
Colchester General Hospital
🇬🇧Colchester, England, United Kingdom
Russells Hall Hospital
🇬🇧Dudley, England, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, England, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, England, United Kingdom
Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
Berkshire Cancer Centre at Royal Berkshire Hospital
🇬🇧Reading, England, United Kingdom
Rotherham General Hospital
🇬🇧Rotherham, England, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, England, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Scotland, United Kingdom
Ayr Hospital
🇬🇧Ayr, Scotland, United Kingdom
Ninewells Hospital
🇬🇧Dundee, Scotland, United Kingdom
Crosshouse Hospital
🇬🇧Kilmarnock, Scotland, United Kingdom
Guy's Hospital
🇬🇧London, England, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, England, United Kingdom