High-Dose Melphalan and a Second Stem Cell Transplant or Low-Dose Cyclophosphamide in Treating Patients With Relapsed Multiple Myeloma After Chemotherapy

NCT00747877 | Unknown Phase 3

• 5 other identifiers: LCC-HM05/7287CDR0000612567EU-20873ISRCTN60123120EudraCT-2006-005890-24
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 53

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; stage I multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.

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.

Drug: cyclophosphamide

Interventions

cyclophosphamide DRUG

Given orally

Arm II

melphalan DRUG

Given IV

Arm I

autologous hematopoietic stem cell transplantation PROCEDURE

Patients undergo autologous hematopoietic stem cell transplantation on day 0.

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Leeds Cancer Centre at St. James's University Hospital: lead

Study Sites (53)

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, RG24 9NA, United Kingdom

RECRUITING

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TH, United Kingdom

RECRUITING

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

RECRUITING

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

RECRUITING

Bradford Royal Infirmary

Bradford, England, BD9 6RJ, United Kingdom

RECRUITING

Frenchay Hospital

Bristol, England, BS16 1LE, United Kingdom

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

RECRUITING

St. Helier Hospital

Carshalton, England, SM5 1AA, United Kingdom

RECRUITING

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

RECRUITING

Saint Richards Hospital

Chichester, England, P019 4SE, United Kingdom

RECRUITING

Colchester General Hospital

Colchester, England, CO4 5JL, United Kingdom

RECRUITING

Dorset County Hospital

Dorchester, England, DT1 2JY, United Kingdom

RECRUITING

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

RECRUITING

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

RECRUITING

Gloucestershire Royal Hospital

Gloucester, England, GL1 3NN, United Kingdom

RECRUITING

Ipswich Hospital

Ipswich, England, IP4 5PD, United Kingdom

RECRUITING

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

RECRUITING

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

RECRUITING

Aintree University Hospital

Liverpool, England, L9 7AL, United Kingdom

RECRUITING

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

RECRUITING

Guy's Hospital

London, England, SE1 9RT, United Kingdom

RECRUITING

King's College Hospital

London, England, SE5 9RS, United Kingdom

RECRUITING

St. George's Hospital

London, England, SW17 0QT, United Kingdom

RECRUITING

University College of London Hospitals

London, England, WIT 3AA, United Kingdom

RECRUITING

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

RECRUITING

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

RECRUITING

Arrowe Park Hospital

Metropolitan Borough of Wirral, England, CH49 5PE, United Kingdom

RECRUITING

James Cook University Hospital

Middlesbrough, England, TS4 3BW, United Kingdom

RECRUITING

Royal Victoria Infirmary

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

RECRUITING

Norfolk and Norwich University Hospital

Norwich, England, NR4 7UY, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, England, NG5 1PB, United Kingdom

RECRUITING

Oxford Radcliffe Hospital

Oxford, England, 0X3 9DU, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

RECRUITING

Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, England, RG1 5AN, United Kingdom

RECRUITING

Rotherham General Hospital

Rotherham, England, S60 2UD, United Kingdom

RECRUITING

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

RECRUITING

Royal Hallamshire Hospital

Sheffield, England, S1O 2JF, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

RECRUITING

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

RECRUITING

Musgrove Park Hospital

Taunton, England, TA1 5DA, United Kingdom

RECRUITING

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

RECRUITING

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, BT8 8JR, United Kingdom

RECRUITING

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

RECRUITING

Ayr Hospital

Ayr, Scotland, KA6 6DX, United Kingdom

RECRUITING

Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

RECRUITING

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

RECRUITING

Crosshouse Hospital

Kilmarnock, Scotland, KA2 OBE, United Kingdom

RECRUITING

Pinderfields General Hospital

Wakefield, Scotland, WF1 4DG, United Kingdom

RECRUITING

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

RECRUITING

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

RECRUITING

Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

RECRUITING

Related Publications (5)

• 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.

  PMID: 38195983 DERIVED

• Cook 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.

  PMID: 27374467 DERIVED

• Parrish 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.

  PMID: 26827659 DERIVED

• Cook 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.

  PMID: 24948586 DERIVED

• Michaelis 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.

  PMID: 23298856 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Cyclophosphamide; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Gordon Cook, MD, PhD

  Leeds Cancer Centre at St. James's University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 4, 2008
• First Posted: September 5, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2012
• Last Updated: August 12, 2013

Record last verified: 2009-06

Locations

GB (53)