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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00747877
First received: September 4, 2008
Last updated: August 9, 2013
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: cyclophosphamide
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate to bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) [ Designated as safety issue: No ]
  • Overall response rate following randomized treatments [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Toxicity and safety of autologous stem cell transplantation [ Designated as safety issue: Yes ]
  • Toxicity and safety of weekly cyclophosphamide [ Designated as safety issue: Yes ]
  • Toxicity and safety of PAD therapy [ Designated as safety issue: Yes ]
  • Feasibility of stem cell collection [ Designated as safety issue: No ]
  • Pain [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 460
Study Start Date: April 2008
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive high-dose melphalan IV on day -1 followed by autologous stem cell transplantation (ASCT) on day 0.
Drug: melphalan
Given IV
Procedure: autologous hematopoietic stem cell transplantation
Patients undergo autologous hematopoietic stem cell transplantation on day 0.
Experimental: Arm II
Patients receive low-dose cyclophosphamide IV or orally once a week for 12-20 weeks for a total of 12 courses.
Drug: cyclophosphamide
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00747877

  Hide Study Locations
Locations
United Kingdom
Basingstoke and North Hampshire NHS Foundation Trust Recruiting
Basingstoke, England, United Kingdom, RG24 9NA
Contact: Contact Person    44-125-631-4793      
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust Recruiting
Birmingham, England, United Kingdom, B15 2TH
Contact: Contact Person    44-121-472-1311      
Birmingham Heartlands Hospital Recruiting
Birmingham, England, United Kingdom, B9 5SS
Contact: Contact Person    44-121-424-2000      
Royal Bournemouth Hospital Recruiting
Bournemouth, England, United Kingdom, BH7 7DW
Contact: Contact Person    44-202-303-626      
Bradford Royal Infirmary Recruiting
Bradford, England, United Kingdom, BD9 6RJ
Contact: Contact Person    44-1274-542-200      
Bristol Haematology and Oncology Centre Recruiting
Bristol, England, United Kingdom, BS2 8ED
Contact: Contact Person         
Frenchay Hospital Recruiting
Bristol, England, United Kingdom, BS16 1LE
Contact: Contact Person    44-117-970-1212      
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Contact Person    44-1223-245-151      
St. Helier Hospital Recruiting
Carshalton, England, United Kingdom, SM5 1AA
Contact: Contact Person    44-20-8296-2000      
Gloucestershire Oncology Centre at Cheltenham General Hospital Recruiting
Cheltenham, England, United Kingdom, GL53 7AN
Contact: Contact Person    44-8454-222-222      
Saint Richards Hospital Recruiting
Chichester, England, United Kingdom, P019 4SE
Contact: Contact Person    44-1243-788-122      
Colchester General Hospital Recruiting
Colchester, England, United Kingdom, CO4 5JL
Contact: Contact Person    44-1206-747-474      
Dorset County Hospital Recruiting
Dorchester, England, United Kingdom, DT1 2JY
Contact: Contact Person    44-1305-251-150      
Russells Hall Hospital Recruiting
Dudley, England, United Kingdom, DY1 2HQ
Contact: Contact Person    44-1384-456-111      
Royal Devon and Exeter Hospital Recruiting
Exeter, England, United Kingdom, EX2 5DW
Contact: Contact Person    44-1392-411-611      
Gloucestershire Royal Hospital Recruiting
Gloucester, England, United Kingdom, GL1 3NN
Contact: Contact Person    44-8454-222-222      
Ipswich Hospital Recruiting
Ipswich, England, United Kingdom, IP4 5PD
Contact: Contact Person    44-1473-712-233      
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Contact Person    44-113-206-6400      
Aintree University Hospital Recruiting
Liverpool, England, United Kingdom, L9 7AL
Contact: Contact Person    44-151-525-5980      
Royal Liverpool University Hospital Recruiting
Liverpool, England, United Kingdom, L7 8XP
Contact: Contact Person    44-151-706-2000      
Guy's Hospital Recruiting
London, England, United Kingdom, SE1 9RT
Contact: Contact Person    44-20-7188-7188      
Saint Bartholomew's Hospital Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Contact Person    44-20-7601-8391      
St. George's Hospital Recruiting
London, England, United Kingdom, SW17 0QT
Contact: Contact Person    44-208-672-1255      
King's College Hospital Recruiting
London, England, United Kingdom, SE5 9RS
Contact: Contact Person    44-20-3299-9000      
University College of London Hospitals Recruiting
London, England, United Kingdom, WIT 3AA
Contact: Contact Person    44-20-7636-8333      
Christie Hospital Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Contact Person    44-845-226-3000      
Manchester Royal Infirmary Recruiting
Manchester, England, United Kingdom, M13 9WL
Contact: Contact Person    44-161-276-1234      
James Cook University Hospital Recruiting
Middlesbrough, England, United Kingdom, TS4 3BW
Contact: Contact Person    44-1642-850-850      
Royal Victoria Infirmary Recruiting
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Contact: Contact Person    44-191-233-6161      
Norfolk and Norwich University Hospital Recruiting
Norwich, England, United Kingdom, NR4 7UY
Contact: Contact Person    44-603-286-286      
Nottingham City Hospital Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: Contact Person    44-115-969-1169      
Oxford Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Contact Person    44-1865-64841      
Derriford Hospital Recruiting
Plymouth, England, United Kingdom, PL6 8DH
Contact: Contact Person    44-175-277-7111      
Berkshire Cancer Centre at Royal Berkshire Hospital Recruiting
Reading, England, United Kingdom, RG1 5AN
Contact: Contact Person    44-118-322-7878      
Rotherham General Hospital Recruiting
Rotherham, England, United Kingdom, S60 2UD
Contact: Contact Person    44-1709-820-000      
Salisbury District Hospital Recruiting
Salisbury, England, United Kingdom, SP2 8BJ
Contact: Contact Person    44-1722-336-262      
Royal Hallamshire Hospital Recruiting
Sheffield, England, United Kingdom, S1O 2JF
Contact: Contact Person    44-114-271-1900      
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Contact Person    44-23-8079-8751      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Contact Person    44-20-8642-6011      
Musgrove Park Hospital Recruiting
Taunton, England, United Kingdom, TA1 5DA
Contact: Contact Person    44-1823-333-444      
Torbay Hospital Recruiting
Torquay, England, United Kingdom, TQ2 7AA
Contact: Contact Person    44-1803-614-567      
Arrowe Park Hospital Recruiting
Wirral, England, United Kingdom, CH49 5PE
Contact: Contact Person    44-151-678-5111      
Belfast City Hospital Trust Incorporating Belvoir Park Hospital Recruiting
Belfast, Northern Ireland, United Kingdom, BT8 8JR
Contact: Contact Person    44-2890-699-069      
Aberdeen Royal Infirmary Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Contact: Contact Person    44-84-5456-6000      
Ayr Hospital Recruiting
Ayr, Scotland, United Kingdom, KA6 6DX
Contact: Contact Person    44-1292-610-555      
Ninewells Hospital Recruiting
Dundee, Scotland, United Kingdom, DD1 9SY
Contact: Contact Person    44-1382-660-111      
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Contact Person    44-141-211-2123      
Raigmore Hospital Recruiting
Inverness, Scotland, United Kingdom, 1V2 3UJ
Contact: Contact Person    44-1463-704-000 ext. 4310      
Crosshouse Hospital Recruiting
Kilmarnock, Scotland, United Kingdom, KA2 OBE
Contact: Contact Person    44-1563-521-133      
Pinderfields General Hospital Recruiting
Wakefield, Scotland, United Kingdom, WF1 4DG
Contact: Contact Person    44-84-4811-8110      
Ysbyty Gwynedd Recruiting
Bangor, Wales, United Kingdom, LL57 2PW
Contact: Contact Person    44-1248-370-007      
Glan Clwyd Hospital Recruiting
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Contact: Contact Person    44-1745-583-910      
Singleton Hospital Recruiting
Swansea, Wales, United Kingdom, SA2 8QA
Contact: Contact Person    44-1792-285-501      
Sponsors and Collaborators
Leeds Cancer Centre at St. James's University Hospital
Investigators
Principal Investigator: Gordon Cook, MD, PhD Leeds Cancer Centre at St. James's University Hospital
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00747877     History of Changes
Other Study ID Numbers: LCC-HM05/7287, CDR0000612567, EU-20873, ISRCTN60123120, EudraCT-2006-005890-24
Study First Received: September 4, 2008
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
stage I multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 21, 2014