Contact information
Type
Scientific
Primary contact
Dr H.M. Lokhorst
ORCID ID
Contact details
University Medical Center Utrecht
Department of Hematology
P.O. Box 85500
Utrecht
3508 GA
Netherlands
+31 (0)30 2507230
h.lokhorst@digd.azu.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Ho24
Study information
Scientific title
Acronym
HOVON 24 MM
Study hypothesis
The hypothesis to be tested is that the outcome in arm II (and Allogeneic Bone Marrow Transplant [ABMT]) is better than in arm I.
Objectives:
1. Evaluation of the effect of myeloablative chemo-/radiotherapy and autologous stem cell transplantation in comparison with chemotherapy alone with respect to the mentioned endpoints
2. Assessment of the value of risk factors at diagnosis with dose intensity of treatment
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Multicentre, randomised, active controlled, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Multiple Myeloma
Intervention
Patients will be treated with 3 x VAD (vincristine, doxorubicine, dexamethasone). Patients less than or equal to 55 years with a Human Leukocyte Antigen (HLA) identical sibling will proceed to Allo BMT. All other eligible patients will be randomised between:
1. Arm I: PBSC pheresis after cyclophosphamide priming (cyclophosphamide, mesnum, G-CSF), IDM (melphalan, G-CSF) every 8 weeks 2 courses. In case of PR/CR maintenance therapy with IFN-alpha-2a until relapse. PBSCT may be performed after reinduction or relapse
2. Arm II: PBSC pheresis after cyclophosphamide priming (cyclophosphamide, mesnum, G-CSF), IDM (melphalan, G-CSF) q 8 weeks 2 courses. In case of PR/CR intensive treatment with cyclophosphamide/TBI and autologous transplantation, maintenance with IFN-alpha-2a until relapse
Intervention type
Drug
Phase
Phase III
Drug names
Vincristine, doxorubicine, dexamethasone (VAD), cyclophosphamide, mesnum, Granulocyte Colony Stimulating Factor (G-CSF), melphalan
Primary outcome measure
Remission rate.
Secondary outcome measures
1. Event-free survival
2. Overall survival
3. Quality of life
4. Cost-benefit
Overall trial start date
07/11/1995
Overall trial end date
01/04/2000
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
At entry:
1. Previously untreated multiple myeloma, stage 2 or 3 according to Salmon and Durie
2. Aged less than 66 years
3. World Health Organization (WHO) performance status 0 - 3
4. Informed consent
For Interferon (IFN) maintenance and Peripheral Blood Stem Cell Transplant (PBSCT) or Allogeneic Bone Marrow Transplant (ABMT):
1. At least Partial Remission (PR) after induction therapy
2. WHO performance status 0 - 2
3. Suitable peripheral stem or bone marrow graft
4. No active infections
5. Absence of severe cardiac, pulmonary, neurologic, psychiatric disease
6. Serum creatinine, bilirubin and transaminases of less than 2.5 x upper limit of normal values
7. Platelet count greater than 50 x 10^9/l
8. Absolute neutrophil count greater than 1 x 10^9/l
9. Informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
452
Participant exclusion criteria
At entry:
1. Received more than 2 courses of melphalan, prednisone or vincristine, melphalan (M), cyclophosphamide, prednisone (VMCP)
2. Severe cardiac disease (= severe heart failure requiring symptomatic treatment or a cardiac ejection fraction of less than 45% with presence of normal hemoglobin), severe pulmonary, neurologic or metabolic disease- Inadequate liver function, i.e., bilirubin greater than or equal to 25 x upper normal value
3. Prior malignancies except non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
4. Prior extensive radiotherapy involving the myelum (precluding total body irradiation)
Recruitment start date
07/11/1995
Recruitment end date
01/04/2000
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Center Utrecht,
Utrecht
3508 GA
Netherlands
Sponsor information
Organisation
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (Netherlands)
Sponsor details
Vrije University Medical Centre (VUMC)
PO Box 7057
Amsterdam
1007 MB
Netherlands
+31 (0)20 444 2693
hdc@hovon.nl
Sponsor type
Research organisation
Website
Funders
Funder type
Industry
Funder name
Roche Nederland B.V. (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Amgen (The Netherlands)
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Funder name
Johnson & Johnson (The Netherlands)
Alternative name(s)
Johnson & Johnson, JNJ
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Funder name
Commission for Medical Applied Research (Commissie voor Klinisch Toegepast Onderzoek [CKTO]) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Novartis Pharma B.V. (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
Results in:
1. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12456509
2. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12721248
3. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15110879
Publication citations
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Segeren CM, Sonneveld P, van der Holt B, Vellenga E, Croockewit AJ, Verhoef GE, Cornelissen JJ, Schaafsma MR, van Oers MH, Wijermans PW, Fibbe WE, Wittebol S, Schouten HC, van Marwijk Kooy M, Biesma DH, Baars JW, Slater R, Steijaert MM, Buijt I, Lokhorst HM, , Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study., Blood, 2003, 101, 6, 2144-2151, doi: 10.1182/blood-2002-03-0889.
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Lokhorst HM, Segeren CM, Verdonck LF, van der Holt B, Raymakers R, van Oers MH, Barge RM, Schouten HC, Westveer PH, Steijaert MM, Cornelissen JJ, Sonneveld P, , Partially T-cell-depleted allogeneic stem-cell transplantation for first-line treatment of multiple myeloma: a prospective evaluation of patients treated in the phase III study HOVON 24 MM., J. Clin. Oncol., 2003, 21, 9, 1728-1733, doi: 10.1200/JCO.2003.04.033.
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van Agthoven M, Segeren CM, Buijt I, Uyl-de Groot CA, van der Holt B, Lokhorst HM, Sonneveld P, A cost-utility analysis comparing intensive chemotherapy alone to intensive chemotherapy followed by myeloablative chemotherapy with autologous stem-cell rescue in newly diagnosed patients with stage II/III multiple myeloma; a prospective randomised phase III study., Eur. J. Cancer, 2004, 40, 8, 1159-1169, doi: 10.1016/j.ejca.2004.01.019.