AzTrials
AzTrials

Multiple Myeloma and Plasma Cell NeoplasmPhase 3NCT00028886

Combination Chemotherapy With or Without Thalidomide in Treating Patients With Multiple Myeloma

A Phase 3 study testing filgrastim, recombinant interferon alfa and cyclophosphamide in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Commissie Voor Klinisch Toegepast Onderzoek at 17 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
filgrastim, recombinant interferon alfa and cyclophosphamide
Type of treatment
Surgery or procedure
How many people
450 participants
Where
17 sitesin 2 countries
Study dates
Mar 2001to not given
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed multiple myeloma
  • Stage II or III
  • No systemic amyloid light-chain amyloidosis

PATIENT CHARACTERISTICS:

Age:

  • 18 to 65

Performance status:

  • WHO 0-3

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • No significant hepatic dysfunction*
  • Bilirubin less than 1.75 mg/dL*
  • AST/ALT less than 2.5 times normal* NOTE: *Unless related to myeloma

Renal:

  • Not specified

Cardiovascular:

  • No severe cardiac dysfunction
  • No New York Heart Association class II, III, or IV heart disease

Other:

  • HIV negative
  • No active uncontrolled infection
  • No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
  • No known intolerance to thalidomide
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Patients 18 to 55 years of age must not have been allocated before study randomization to allogeneic stem cell transplantation with an HLA-identical sibling donor

Chemotherapy:

  • No more than 2 prior courses of melphalan and prednisone therapy for local myeloma progression
  • No other prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Prior local radiotherapy for local myeloma progression allowed
  • No other prior radiotherapy

Surgery:

  • Not specified

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

Netherlands16 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5211 NL

  • Meander Medisch Centrum

    Amersfoort, 3816 CP

  • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

    Amsterdam, 1066 CX

  • Vrije Universiteit Medisch Centrum

    Amsterdam, 1081HV

  • Academisch Medisch Centrum at University of Amsterdam

    Amsterdam, 1105 AZ

  • Medisch Spectrum Twente

    Enschede, 7500 KA

  • University Medical Center Groningen

    Groningen, 9713 EZ

  • Medisch Centrum Leeuwarden - Zuid

    Leeuwarden, 8934 AD

  • Leiden University Medical Center

    Leiden, 2300 RC

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6202 AZ

  • Sint Antonius Ziekenhuis

    Nieuwegein, 3435 CM

  • Universitair Medisch Centrum St. Radboud - Nijmegen

    Nijmegen, NL-6500 HB

  • Daniel Den Hoed Cancer Center at Erasmus Medical Center

    Rotterdam, 3008 AE

  • HagaZiekenhuis - Locatie Leyenburg

    The Hague, 2545 CH

  • University Medical Center Utrecht

    Utrecht, 3584 CX

  • Isala Klinieken - locatie Sophia

    Zwolle, 8000 GK

Other trials in Netherlands

Belgium1 site

  • U.Z. Gasthuisberg

    Leuven, B-3000

Other trials in Belgium

About this study

Official 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

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect). It is not yet known whether chemotherapy followed by peripheral blood stem cell transplant is more effective with or without thalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with thalidomide to see how well it works compared with giving combination chemotherapy without thalidomide in treating patients with multiple myeloma.

Read the detailed description

OBJECTIVES:

  • Compare the efficacy of doxorubicin, dexamethasone, and high-dose melphalan with versus without thalidomide, in terms of event-free survival, of patients with multiple myeloma.
  • Determine the response rate, complete response rate, overall survival, and progression-free survival of patients treated with these regimens.
  • Determine the safety and toxicity of thalidomide in combination with intensive chemotherapy in these patients.
  • Assess the value of prognostic factors at diagnosis in individual patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and treatment policy (1 course vs 2 courses of high-dose melphalan). Patients are randomized to 1 of 2 treatment arms.

Arm I:

  • Patients receive induction chemotherapy (AD) comprising doxorubicin IV on days 1-4 and oral dexamethasone on days 1-4, 9-12, and 17-20. Patients receive oral thalidomide daily beginning on day 1 and continuing until 2 weeks before start of stem cell mobilization. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Patients receive stem cell mobilization with chemotherapy comprising cyclophosphamide IV on day 1 and doxorubicin IV and oral dexamethasone on days 1-4 (CAD). Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until last apheresis.
  • Beginning 8-10 weeks after stem cell collection, patients receive low-dose oral thalidomide daily and high-dose melphalan IV on days -3 and -2 as intensification. Patients undergo stem cell infusion on day 0. Patients may receive a second course of high-dose melphalan 2-3 months after the first course, in which case, stem cell infusion follows the second course of melphalan.
  • Patients receive maintenance therapy with oral thalidomide daily until disease progression or after 3 months if no response.
  • Beginning 2 months after the last course, patients with an HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation after radiotherapy.

Arm II:

  • Patients receive induction chemotherapy (VAD) comprising vincristine IV and doxorubicin IV on days 1-4 and dexamethasone on days 1-4, 9-12, and 17-20. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Patients receive stem cell mobilization with CAD chemotherapy as in arm I. G-CSF is given as in arm I.
  • Patients receive high-dose melphalan and undergo stem cell infusion as in arm I.
  • Patients receive maintenance therapy with interferon alfa SC 3 times weekly until progression or after 3 months if no partial response.
  • Beginning 2 months after the last course, patients with an HLA-identical sibling donor undergo nonmyeloablative stem cell transplantation after radiotherapy.

All patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 4 years.

Being tested
filgrastim, recombinant interferon alfa, cyclophosphamide, dexamethasone, doxorubicin hydrochloride
Keywords
stage II multiple myeloma, stage III multiple myeloma
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

Secondary outcomes (4)

  1. Partial response and complete response

  2. Overall survival

  3. Progression-free survival

  4. Toxicity

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMar 2001

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Enrolment
450 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00028886
Sponsor's protocol ID
CDR0000069144
Other IDs
CKTO-2001-02, HOVON-50MM, EU-20133, HOVON-CKVO-2001-02
Status last verified
Oct 2012
First submitted
4 Jan 2002
Last updated
17 Sep 2013
Results posted
No

Publications

  • Johnson DC, Corthals S, Ramos C, Hoering A, Cocks K, Dickens NJ, Haessler J, Goldschmidt H, Child JA, Bell SE, Jackson G, Baris D, Rajkumar SV, Davies FE, Durie BG, Crowley J, Sonneveld P, Van Ness B, Morgan GJ. Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping. Blood. 2008 Dec 15;112(13):4924-34. doi: 10.1182/blood-2008-02-140434. Epub 2008 Sep 19.

    PubMed 18805967

  • Lokhorst HM, van der Holt B, Cornelissen JJ, Kersten MJ, van Oers M, Raymakers R, Minnema MC, Zweegman S, Janssen JJ, Zijlmans M, Bos G, Schaap N, Wittebol S, de Weerdt O, Ammerlaan R, Sonneveld P. Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study. Blood. 2012 Jun 28;119(26):6219-25; quiz 6399. doi: 10.1182/blood-2011-11-393801. Epub 2012 Mar 22.

    PubMed 22442350

  • Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. doi: 10.1182/blood-2009-05-222539. Epub 2009 Oct 30.

    PubMed 19880501

  • Lokhorst HM, Schmidt-Wolf I, Sonneveld P, van der Holt B, Martin H, Barge R, Bertsch U, Schlenzka J, Bos GM, Croockewit S, Zweegman S, Breitkreutz I, Joosten P, Scheid C, van Marwijk-Kooy M, Salwender HJ, van Oers MH, Schaafsma R, Naumann R, Sinnige H, Blau I, Delforge M, de Weerdt O, Wijermans P, Wittebol S, Duersen U, Vellenga E, Goldschmidt H; Dutch-Belgian HOVON; German GMMG. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma. Haematologica. 2008 Jan;93(1):124-7. doi: 10.3324/haematol.11644.

    PubMed 18166796

  • Lokhorst H, van der Holt B, Zweegman S, et al.: Final analysis of HOVON-50 randomized phase III study on the effect of thalidomide combined with adriamycine,dexamethasone (AD) and high dose melphalan (HDM) in patients with multiple myeloma (MM). [Abstract] Blood 112 (11): A-157, 2008.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing filgrastim, recombinant interferon alfa and cyclophosphamide in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Commissie Voor Klinisch Toegepast Onderzoek at 17 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00028886, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in