Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
09/11/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.hovon.nl

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 measures

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

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

http://www.hovon.nl/

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

Results - basic reporting

Publication summary

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes