A randomized phase III study on the effect of Thalidomide combined with Adriamycin, Dexamethasone (AD) and High Dose Melphalan in patients with multiple myeloma.

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR238
• Date of registration: 06/09/2005
• Primary sponsor: Erasmus Medical Center, Daniel den Hoed Cancer Center
• Public title: A randomized phase III study on the effect of Thalidomide combined with Adriamycin, Dexamethasone (AD) and High Dose Melphalan in patients with multiple myeloma.
• Scientific title: A randomized phase III study on the effect of Thalidomide combined with Adriamycin, Dexamethasone (AD) and High Dose Melphalan in patients with multiple myeloma. - HOVON 50 MM / GMMG-HD3
• Date of first enrolment: 27/11/2001
• Target sample size: 450
• Recruitment status: complete
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=238
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Active; Group: Parallel; Type: 2 or more arms, randomized

Countries of recruitment

The Netherlands

Contacts

• Name: H.M. Lokhorst

• Name: H.M. Lokhorst

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon & Durie criteria;

2. Age 18-65 years inclusive;

3. WHO performance status 0-3;

4. Negative pregnancy test at inclusion if applicable;

5. Written informed consent.
Exclusion criteria: 1. Known intolerance of Thalidomide;

2. Systemic AL amyloidosis;

3. Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone or local radiotherapy in case of local myeloma progression;

4. Severe cardiac dysfunction (NYHA classification II-IV);

5. Significant hepatic dysfunction (serum bilirubin >= 30 micromol/l or transaminases >= 2.5 times normal level), unless related to myeloma;

6. Patients known to be HIV-positive;

7. Patients with active, uncontrolled infections;

8. Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;

9. Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);

10. Patients <= 55 years with an HLA-identical sibling who will undergo myeloablative AlloSCT.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Multiple myeloma (Kahler's disease)

Intervention(s)

Patients with multiple myeloma, meeting all eligibility criteria will be randomized on entry between:

Arm A:
standard Vincristine, Adriamycin and Dexamethasone (VAD) induction, followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance therapy with alpha-interferon.


Arm B:

induction chemotherapy with Thalidomide, Adriamycin and Dexamethasone (TAD) followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance with Thalidomide.

Primary Outcome(s)

Event free survival (i.e., time from registration to induction failure, progression or death, whichever occurs first); the time to failure of patients with induction failure is set at one day.

Patients are considered induction failure when they have not achieved at least a PR and are not eligible for further treatment according to protocol.

Secondary Outcome(s)

1. Response (PR and CR);

2. Overall survival measured form the time of registration. Patient still alive or lost to follow up are censored at the date they were last known to be alive;

3. Progression free survival (duration of the first response (PR or CR)) measured from the time of achievement of PR (or CR) to date of progression or death from any cause (whichever occurs first);

4. Toxicities of Thalidomide and chemotherapy.

Secondary ID(s)

HO50

ISRCTN06413384

Source(s) of Monetary Support

Koningin Wilhelmina Fonds (KWF), Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)

Secondary Sponsor(s)

VU University Medical Center, Dutch haemato-oncology association (Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)