A randomised phase III study on the effect of bortezomib combined with adriamycin, dexamethasone (AD) for induction treatment, followed by high dose melphalan and bortezomib alone during maintenance in patients with multiple myeloma

ISRCTN	ISRCTN64455289
DOI	https://doi.org/10.1186/ISRCTN64455289
Clinical Trials Information System (CTIS)	2004-000944-26
Protocol serial number	26866138MMY3003; HO65
Sponsor	Dutch Haemato-oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland [HOVON])
Funders	Johnson & Johnson, Amgen, Chugai, Novartis, Roche, German Federal Ministry of Education and Research

Submission date: 13/09/2005
Registration date: 03/11/2005
Last edited: 03/09/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Pieter Sonneveld
Scientific

Erasmus MC
Dept of Hematology
P.O. Box 2040
Rotterdam
3000 CA
Netherlands

Email	p.sonneveld@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Prospective, multicentre, randomised, active controlled, parallel group trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	HOVON65/GMMG-HD4
Study objectives	Bortezomib combined with intensive chemotherapy and in maintenance therapy is superior in comparison with intensive therapy with vincristine followed by thalidomide maintenance in patients with previously untreated multiple myeloma, as measured by response rate and progression-free and overall survival.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Multiple myeloma
Intervention	Arm A: Standard Vincristine, Adriamycin and Dexamethasone (VAD) induction, followed by intensive chemotherapy with melphalan 200 mg/m^2 and autologous blood stem cell transplantation, followed by maintenance therapy with thalidomide. Arm B: Induction chemotherapy with Bortezomib, Adriamycin and Dexamethasone (BAD) followed by intensive chemotherapy with melphalan 200 mg/m^2 and autologous blood stem cell transplantation, followed by maintenance with bortezomib. Duration of treatment: Expected duration of induction, stem cell collection and intensification (with or without Bortezomib) is six to seven months. Maintenance therapy with Bortezomib or Thalidomide will be given for two years. Please note that the anticipated end date of this trial has been shortened to 22nd April 2007.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Bortezomib, vincristine, adriamycin, dexamethasone and melphalan
Primary outcome measure(s)	Progression Free Survival (PFS), i.e. time from registration to progression, relapse or death from any cause.
Key secondary outcome measure(s)	1. Response (Partial Remission [PR], very Good Partial Remission [vGPR] and Complete Remission [CR]) 2. Overall Survival (OS) 3. PFS from High-Dose Therapy (HDT) i.e. time from last High-Dose Melphalan (HDM) treatment to progression, relapse or death from any cause whichever occurs first for patients who received at least PR on HDT 4. Toxicity 5. PFS analysed as primary endpoint, but patients with an allogeneic transplant not censored. This primarily to check whether censoring has a major impact.
Completion date	30/09/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	800
Key inclusion criteria	1. Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon and Durie criteria 2. Age 18 to 65 years inclusive 3. World Health Organisation (WHO) performance status zero to three (WHO = three is allowed only when caused by multiple myeloma and not by co-morbid conditions) 4. Negative pregnancy test at inclusion if applicable 5. Written informed consent
Key exclusion criteria	1. Known intolerance of thalidomide or boron 2. Systemic AL amyloidosis 3. Non-secretory multiple myeloma 4. Previous chemotherapy or radiotherapy except two cycles of melphalan/prednisone or local radiotherapy in case of local myeloma progression 5. Severe cardiac dysfunction (New York Heart Association [NYHA] classification II - IV) 6. Significant hepatic dysfunction (serum bilirubin more than or equal to 30 µmol/l or transaminases more than or equal to 2.5 times normal level), unless related to myeloma 7. Patients known to be Human Immunodeficiency Virus (HIV) positive 8. Patients with active, uncontrolled infections 9. Patients with neuropathy, CTC grade two or higher 10. Patients with a history of active malignancy during the past five years with the exception of basal carcinoma of the skin or stage zero cervical carcinoma 11. Patients who will not give permission for collection of Bone Marrow (BM) aspirate at entry 12. Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women) 13. Patients 65 years or less with a Human Leukocyte Antigen (HLA) identical sibling who will undergo non-myeloablative AlloSCT 14. Lactating women
Date of first enrolment	01/05/2005
Date of final enrolment	30/09/2011

Locations

Countries of recruitment

Germany
Netherlands

Study participating centre

Erasmus MC

Rotterdam
3000 CA
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2011		Yes	No
Results article	results	26/01/2012		Yes	No
Results article	results	24/01/2013		Yes	No
Results article	results	01/01/2014		Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes