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

NCT00028886 | Unknown Phase 3

• 5 other identifiers: CDR0000069144CKTO-2001-02HOVON-50MMEU-20133HOVON-CKVO-2001-02
• Study Type: interventional
• Target: 450
• Locations: 2 countries
• Sites: 17

Brief 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. 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Event-free survival

Secondary Outcomes (4)

• Partial response and complete response

• Overall survival

• Progression-free survival

• Toxicity

Interventions

filgrastim BIOLOGICAL

recombinant interferon alfa BIOLOGICAL

cyclophosphamide DRUG

dexamethasone DRUG

doxorubicin hydrochloride DRUG

melphalan DRUG

thalidomide DRUG

vincristine sulfate DRUG

bone marrow ablation with stem cell support PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Commissie Voor Klinisch Toegepast Onderzoek: lead

Study Sites (17)

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5211 NL, Netherlands

Location

Meander Medisch Centrum

Amersfoort, 3816 CP, Netherlands

Location

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066 CX, Netherlands

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1081HV, Netherlands

Location

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7500 KA, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 EZ, Netherlands

Location

Medisch Centrum Leeuwarden - Zuid

Leeuwarden, 8934 AD, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, NL-6500 HB, Netherlands

Location

Daniel Den Hoed Cancer Center at Erasmus Medical Center

Rotterdam, 3008 AE, Netherlands

Location

HagaZiekenhuis - Locatie Leyenburg

The Hague, 2545 CH, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Isala Klinieken - locatie Sophia

Zwolle, 8000 GK, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 18805967 BACKGROUND

• 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.

  PMID: 22442350 RESULT

• 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.

  PMID: 19880501 RESULT

• 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.

  PMID: 18166796 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Filgrastim; Interferon-alpha; Cyclophosphamide; Dexamethasone; Doxorubicin; Melphalan; Thalidomide; Vincristine; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interferon Type I; Interferons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• H. Lokhorst, MD, PhD

  UMC Utrecht

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 4, 2002
• First Posted: January 27, 2003
• Study Start: March 1, 2001
• Last Updated: September 17, 2013

Record last verified: 2012-10

Locations

NL (16); BE (1)