Combination Chemotherapy With or Without Thalidomide in Treating Patients With Multiple Myeloma
NCT ID: NCT00028886
Last Updated: 2013-09-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
450 participants
INTERVENTIONAL
2001-03-31
Brief Summary
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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.
Detailed Description
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* 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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
TREATMENT
Interventions
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filgrastim
recombinant interferon alfa
cyclophosphamide
dexamethasone
doxorubicin hydrochloride
melphalan
thalidomide
vincristine sulfate
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Eligibility Criteria
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Inclusion Criteria
* 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
18 Years
65 Years
ALL
No
Sponsors
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Commissie Voor Klinisch Toegepast Onderzoek
OTHER
Principal Investigators
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H. Lokhorst, MD, PhD
Role: STUDY_CHAIR
UMC Utrecht
Locations
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U.Z. Gasthuisberg
Leuven, , Belgium
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, , Netherlands
Meander Medisch Centrum
Amersfoort, , Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, , Netherlands
Vrije Universiteit Medisch Centrum
Amsterdam, , Netherlands
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, , Netherlands
Medisch Spectrum Twente
Enschede, , Netherlands
University Medical Center Groningen
Groningen, , Netherlands
Medisch Centrum Leeuwarden - Zuid
Leeuwarden, , Netherlands
Leiden University Medical Center
Leiden, , Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, , Netherlands
Sint Antonius Ziekenhuis
Nieuwegein, , Netherlands
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, , Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Rotterdam, , Netherlands
HagaZiekenhuis - Locatie Leyenburg
The Hague, , Netherlands
University Medical Center Utrecht
Utrecht, , Netherlands
Isala Klinieken - locatie Sophia
Zwolle, , Netherlands
Countries
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References
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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.
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.
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.
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.
Other Identifiers
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CKTO-2001-02
Identifier Type: -
Identifier Source: secondary_id
HOVON-50MM
Identifier Type: -
Identifier Source: secondary_id
EU-20133
Identifier Type: -
Identifier Source: secondary_id
HOVON-CKVO-2001-02
Identifier Type: -
Identifier Source: secondary_id
CDR0000069144
Identifier Type: -
Identifier Source: org_study_id