Combination Chemotherapy With or Without Thalidomide in Treating 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.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

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

• BACKGROUNDJohnson 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. PMID 18805967
• RESULTLokhorst 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. PMID 22442350
• RESULTLokhorst 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. PMID 19880501
• RESULTLokhorst 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. PMID 18166796
• RESULTLokhorst 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.