Multiple Myeloma and Plasma Cell NeoplasmPhase 3NCT00747877
High-Dose Melphalan and a Second Stem Cell Transplant or Low-Dose Cyclophosphamide in Treating Patients With Relapsed Multiple Myeloma After Chemotherapy
A Phase 3 study testing cyclophosphamide, melphalan and autologous hematopoietic stem cell transplantation in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Leeds Cancer Centre at St. James's University Hospital at 53 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- cyclophosphamide, melphalan and autologous hematopoietic stem cell transplantation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 460 participants
- Where
- 53 sitesUnited Kingdom
- Study dates
- Apr 2008to Apr 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of relapsed multiple myeloma
- Symptomatic disease, including non-secretory
- Previously treated with standard chemotherapy and autologous stem cell transplantation
- Requires therapy for first progressive disease AND at least 18 months since first stem cell transplantation
- Patients who were previously immunofixation-negative and are now immunofixation-positive must have > 5 g/L absolute increase in paraprotein
- Registered in the Myeloma X Relapse (Intensive) Trial and received 2-4 courses of PAD re-induction chemotherapy according to the protocol (consolidation phase)
- Adequate stem cell mobilization available for transplantation defined as ≥ 2x10^6 CD34 + cells/kg or ≥ 2x10^8 PBMC/kg including cells stored from a previous harvest (consolidation phase)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1 x 10^9/L
- Platelet count ≥ 50 x 10^9/L
- Creatinine clearance ≥ 30 mL/min
- Total bilirubin < 2 times upper limit of normal (ULN)
- ALT or AST < 2.5 times ULN
- History of pulmonary disease allowed provided carbon monoxide diffusion in the lungs (KCO/DLCO) is ≥ 50% and/or no requirement for supplementary continuous oxygen
- Left ventricular ejection fraction ≥ 40% by ECG or MUGA scan
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- No peripheral neuropathy ≥ grade 2
- No known HIV or Hepatitis B or C positivity (testing is not required)
- No known resistance to combined bortezomib, doxorubicin hydrochloride, and dexamethasone therapy
- No known history of allergy to compounds containing boron or mannitol
- No other previous or concurrent malignancies except for appropriately treated localized epithelial skin cancer or carcinoma in situ of the cervix, or remote histories of other cured tumors within the past 5 years
- No medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient's participation in the study
- No other contra-indication to treatment that would make the patient ineligible for consolidation phase
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No other prior therapy for relapsed disease except for local radiotherapy, therapeutic plasma exchange, or ≤ 200 mg of dexamethasone
- Radiotherapy since prior transplantation sufficient to alleviate or control pain of local invasion is permitted
- No hemi-body radiation since prior transplantation (consolidation phase)
- At least 4 weeks since prior and no concurrent investigational drugs
Trial locations and contacts
53 sites in 1 country.
53 sites in 1 country
United Kingdom53 sites, 53 recruiting
- Recruiting
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN
Contact Person, 44-84-5456-6000
- Recruiting
Ayr Hospital
Ayr, Scotland, KA6 6DX
Contact Person, 44-1292-610-555
- Recruiting
Ysbyty Gwynedd
Bangor, Wales, LL57 2PW
Contact Person, 44-1248-370-007
- Recruiting
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, England, RG24 9NA
Contact Person, 44-125-631-4793
- Recruiting
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Belfast, Northern Ireland, BT8 8JR
Contact Person, 44-2890-699-069
- Recruiting
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England, B15 2TH
Contact Person, 44-121-472-1311
- Recruiting
Birmingham Heartlands Hospital
Birmingham, England, B9 5SS
Contact Person, 44-121-424-2000
- Recruiting
Royal Bournemouth Hospital
Bournemouth, England, BH7 7DW
Contact Person, 44-202-303-626
- Recruiting
Bradford Royal Infirmary
Bradford, England, BD9 6RJ
Contact Person, 44-1274-542-200
- Recruiting
Frenchay Hospital
Bristol, England, BS16 1LE
Contact Person, 44-117-970-1212
- Recruiting
Bristol Haematology and Oncology Centre
Bristol, England, BS2 8ED
Contact Person
- Recruiting
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ
Contact Person, 44-1223-245-151
- Recruiting
St. Helier Hospital
Carshalton, England, SM5 1AA
Contact Person, 44-20-8296-2000
- Recruiting
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, GL53 7AN
Contact Person, 44-8454-222-222
- Recruiting
Saint Richards Hospital
Chichester, England, P019 4SE
Contact Person, 44-1243-788-122
- Recruiting
Colchester General Hospital
Colchester, England, CO4 5JL
Contact Person, 44-1206-747-474
- Recruiting
Dorset County Hospital
Dorchester, England, DT1 2JY
Contact Person, 44-1305-251-150
- Recruiting
Russells Hall Hospital
Dudley, England, DY1 2HQ
Contact Person, 44-1384-456-111
- Recruiting
Ninewells Hospital
Dundee, Scotland, DD1 9SY
Contact Person, 44-1382-660-111
- Recruiting
Royal Devon and Exeter Hospital
Exeter, England, EX2 5DW
Contact Person, 44-1392-411-611
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G12 0YN
Contact Person, 44-141-211-2123
- Recruiting
Gloucestershire Royal Hospital
Gloucester, England, GL1 3NN
Contact Person, 44-8454-222-222
- Recruiting
Raigmore Hospital
Inverness, Scotland, 1V2 3UJ
Contact Person, 44-1463-704-000 ext. 4310
- Recruiting
Ipswich Hospital
Ipswich, England, IP4 5PD
Contact Person, 44-1473-712-233
- Recruiting
Crosshouse Hospital
Kilmarnock, Scotland, KA2 OBE
Contact Person, 44-1563-521-133
- Recruiting
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Contact Person, 44-113-206-6400
- Recruiting
Royal Liverpool University Hospital
Liverpool, England, L7 8XP
Contact Person, 44-151-706-2000
- Recruiting
Aintree University Hospital
Liverpool, England, L9 7AL
Contact Person, 44-151-525-5980
- Recruiting
Saint Bartholomew's Hospital
London, England, EC1A 7BE
Contact Person, 44-20-7601-8391
- Recruiting
Guy's Hospital
London, England, SE1 9RT
Contact Person, 44-20-7188-7188
- Recruiting
King's College Hospital
London, England, SE5 9RS
Contact Person, 44-20-3299-9000
- Recruiting
St. George's Hospital
London, England, SW17 0QT
Contact Person, 44-208-672-1255
- Recruiting
University College of London Hospitals
London, England, WIT 3AA
Contact Person, 44-20-7636-8333
- Recruiting
Manchester Royal Infirmary
Manchester, England, M13 9WL
Contact Person, 44-161-276-1234
- Recruiting
Christie Hospital
Manchester, England, M20 4BX
Contact Person, 44-845-226-3000
- Recruiting
Arrowe Park Hospital
Metropolitan Borough of Wirral, England, CH49 5PE
Contact Person, 44-151-678-5111
- Recruiting
James Cook University Hospital
Middlesbrough, England, TS4 3BW
Contact Person, 44-1642-850-850
- Recruiting
Royal Victoria Infirmary
Newcastle upon Tyne, England, NE1 4LP
Contact Person, 44-191-233-6161
- Recruiting
Norfolk and Norwich University Hospital
Norwich, England, NR4 7UY
Contact Person, 44-603-286-286
- Recruiting
Nottingham City Hospital
Nottingham, England, NG5 1PB
Contact Person, 44-115-969-1169
- Recruiting
Oxford Radcliffe Hospital
Oxford, England, 0X3 9DU
Contact Person, 44-1865-64841
- Recruiting
Derriford Hospital
Plymouth, England, PL6 8DH
Contact Person, 44-175-277-7111
- Recruiting
Berkshire Cancer Centre at Royal Berkshire Hospital
Reading, England, RG1 5AN
Contact Person, 44-118-322-7878
- Recruiting
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, LL 18 5UJ
Contact Person, 44-1745-583-910
- Recruiting
Rotherham General Hospital
Rotherham, England, S60 2UD
Contact Person, 44-1709-820-000
- Recruiting
Salisbury District Hospital
Salisbury, England, SP2 8BJ
Contact Person, 44-1722-336-262
- Recruiting
Royal Hallamshire Hospital
Sheffield, England, S1O 2JF
Contact Person, 44-114-271-1900
- Recruiting
Southampton General Hospital
Southampton, England, SO16 6YD
Contact Person, 44-23-8079-8751
- Recruiting
Royal Marsden - Surrey
Sutton, England, SM2 5PT
Contact Person, 44-20-8642-6011
- Recruiting
Singleton Hospital
Swansea, Wales, SA2 8QA
Contact Person, 44-1792-285-501
- Recruiting
Musgrove Park Hospital
Taunton, England, TA1 5DA
Contact Person, 44-1823-333-444
- Recruiting
Torbay Hospital
Torquay, England, TQ2 7AA
Contact Person, 44-1803-614-567
- Recruiting
Pinderfields General Hospital
Wakefield, Scotland, WF1 4DG
Contact Person, 44-84-4811-8110
About this study
Official title: Myeloma X Relapse (Intensive): 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.
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.
Read the 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.
- Being tested
- cyclophosphamide, melphalan, autologous hematopoietic stem cell transplantation
- Keywords
- stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage I multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Given orally
melphalanDrug
Given IV
autologous hematopoietic stem cell transplantationProcedure or surgery
Patients undergo autologous hematopoietic stem cell transplantation on day 0.
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0. Receives: Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation |
| Arm II | Experimental | Patients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses. Receives: Drug: cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to disease progression
Secondary outcomes (10)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2008 (estimated)
- Study startApr 2008
- Primary completionApr 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leeds Cancer Centre at St. James's University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Gordon Cook, MD, PhD, Principal investigator, Leeds Cancer Centre at St. James's University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00747877
- Sponsor's protocol ID
- LCC-HM05/7287
- Other IDs
- CDR0000612567, EU-20873, ISRCTN60123120, EudraCT-2006-005890-24
- Status last verified
- Jun 2009
- First submitted
- 4 Sep 2008
- Last updated
- 12 Aug 2013
- Results posted
- No
Publications
de Tute RM, Cook G, Cairns DA, Brown JM, Cavenagh J, Ashcroft AJ, Snowden JA, Yong K, Tholouli E, Jenner M, Hockaday A, Drayson MT, Morris TCM, Rawstron AC, Owen RG. Impact of minimal residual disease (MRD) in salvage autologous stem cell transplantation for relapsed myeloma: results from the NCRI Myeloma X (intensive) trial. Bone Marrow Transplant. 2024 Mar;59(3):431-434. doi: 10.1038/s41409-023-02164-4. Epub 2024 Jan 9. No abstract available.
PubMed 38195983Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, Snowden JA, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Chown S, Heartin E, O'Connor S, Drayson MT, Hockaday A, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016 Jul;3(7):e340-51. doi: 10.1016/S2352-3026(16)30049-7.
PubMed 27374467Parrish C, Morris CTCM, Williams CD, Cairns DA, Cavenagh J, Snowden JA, Ashcroft J, Cavet J, Hunter H, Bird JM, Chalmers A, Brown JM, Yong K, Schey S, Chown S, Cook G; National Cancer Research Institute Haemato-Oncology Clinical Studies Group. Stem Cell Harvesting after Bortezomib-Based Reinduction for Myeloma Relapsing after Autologous Transplantation: Results from the British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) Trial. Biol Blood Marrow Transplant. 2016 Jun;22(6):1009-1016. doi: 10.1016/j.bbmt.2016.01.016. Epub 2016 Jan 28.
PubMed 26827659Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, Ashcroft AJ, Fletcher M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Chalmers A, O'Connor S, Drayson MT, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):874-85. doi: 10.1016/S1470-2045(14)70245-1. Epub 2014 Jun 16.
PubMed 24948586Michaelis LC, Saad A, Zhong X, Le-Rademacher J, Freytes CO, Marks DI, Lazarus HM, Bird JM, Holmberg L, Kamble RT, Kumar S, Lill M, Meehan KR, Saber W, Schriber J, Tay J, Vogl DT, Wirk B, Savani BN, Gale RP, Vesole DH, Schiller GJ, Abidi M, Anderson KC, Nishihori T, Kalaycio ME, Vose JM, Moreb JS, Drobyski W, Munker R, Roy V, Ghobadi A, Holland HK, Nath R, To LB, Maiolino A, Kassim AA, Giralt SA, Landau H, Schouten HC, Maziarz RT, Mikhael J, Kindwall-Keller T, Stiff PJ, Gibson J, Lonial S, Krishnan A, Dispenzieri A, Hari P; Plasma Cell Disorders Working Committee of the Center for International Blood and Marrow Transplant Research. Salvage second hematopoietic cell transplantation in myeloma. Biol Blood Marrow Transplant. 2013 May;19(5):760-6. doi: 10.1016/j.bbmt.2013.01.004. Epub 2013 Jan 5.
PubMed 23298856
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myeloma X Relapse (Intensive): 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.
- ClinicalTrials.gov ID
- NCT00747877
- Acronym / sponsor ID
- LCC-HM05/7287
- Keywords
- stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage I multiple myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 460 participants (estimated)
- Lead sponsor
- Leeds Cancer Centre at St. James's University HospitalUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Apr 2012 (estimated)
- First posted
- 5 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: melphalan, Procedure: autologous hematopoietic stem cell transplantationPatients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0. |
| Arm II | Experimental | Drug: cyclophosphamidePatients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideGiven orally | Drug | Arm II |
| melphalanGiven IV | Drug | Arm I |
| autologous hematopoietic stem cell transplantationPatients undergo autologous hematopoietic stem cell transplantation on day 0. | Procedure or surgery | Arm I |
Primary outcome
Time to disease progression
10 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
- Derived from this study: PubMed 38195983de Tute RM, Cook G, Cairns DA, Brown JM, Cavenagh J, Ashcroft AJ, Snowden JA, Yong K, Tholouli E, Jenner M, Hockaday A, Drayson MT, Morris TCM, Rawstron AC, Owen RG. Impact of minimal residual disease (MRD) in salvage autologous stem cell transplantation for relapsed myeloma: results from the NCRI Myeloma X (intensive) trial. Bone Marrow Transplant. 2024 Mar;59(3):431-434. doi: 10.1038/s41409-023-02164-4. Epub 2024 Jan 9. No abstract available.
- Derived from this study: PubMed 27374467Cook G, Ashcroft AJ, Cairns DA, Williams CD, Brown JM, Cavenagh JD, Snowden JA, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Pratt G, Chown S, Heartin E, O'Connor S, Drayson MT, Hockaday A, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016 Jul;3(7):e340-51. doi: 10.1016/S2352-3026(16)30049-7.
- Derived from this study: PubMed 26827659Parrish C, Morris CTCM, Williams CD, Cairns DA, Cavenagh J, Snowden JA, Ashcroft J, Cavet J, Hunter H, Bird JM, Chalmers A, Brown JM, Yong K, Schey S, Chown S, Cook G; National Cancer Research Institute Haemato-Oncology Clinical Studies Group. Stem Cell Harvesting after Bortezomib-Based Reinduction for Myeloma Relapsing after Autologous Transplantation: Results from the British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) Trial. Biol Blood Marrow Transplant. 2016 Jun;22(6):1009-1016. doi: 10.1016/j.bbmt.2016.01.016. Epub 2016 Jan 28.
- Derived from this study: PubMed 24948586Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, Ashcroft AJ, Fletcher M, Parrish C, Yong K, Cavet J, Hunter H, Bird JM, Chalmers A, O'Connor S, Drayson MT, Morris TC; National Cancer Research Institute Haemato-oncology Clinical Studies Group. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jul;15(8):874-85. doi: 10.1016/S1470-2045(14)70245-1. Epub 2014 Jun 16.
- Derived from this study: PubMed 23298856Michaelis LC, Saad A, Zhong X, Le-Rademacher J, Freytes CO, Marks DI, Lazarus HM, Bird JM, Holmberg L, Kamble RT, Kumar S, Lill M, Meehan KR, Saber W, Schriber J, Tay J, Vogl DT, Wirk B, Savani BN, Gale RP, Vesole DH, Schiller GJ, Abidi M, Anderson KC, Nishihori T, Kalaycio ME, Vose JM, Moreb JS, Drobyski W, Munker R, Roy V, Ghobadi A, Holland HK, Nath R, To LB, Maiolino A, Kassim AA, Giralt SA, Landau H, Schouten HC, Maziarz RT, Mikhael J, Kindwall-Keller T, Stiff PJ, Gibson J, Lonial S, Krishnan A, Dispenzieri A, Hari P; Plasma Cell Disorders Working Committee of the Center for International Blood and Marrow Transplant Research. Salvage second hematopoietic cell transplantation in myeloma. Biol Blood Marrow Transplant. 2013 May;19(5):760-6. doi: 10.1016/j.bbmt.2013.01.004. Epub 2013 Jan 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, United Kingdom
Gordon Cook, MD, PhD principal investigator
Leeds Cancer Centre at St. James's University Hospital
53 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cyclophosphamide, melphalan and autologous hematopoietic stem cell transplantation in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Leeds Cancer Centre at St. James's University Hospital at 53 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to disease progression. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00747877, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2013.