Efficacy and Safety Study of 3 Thalidomide Doses for the Treatment of Relapsed Refractory Multiple Myeloma

NCT00452569 | Completed Phase 3 DMC

• 1 other identifier: THA PH INT 2005 CL001
• Study Type: interventional
• Target: 499
• Locations: 15 countries
• Sites: 86

Brief Summary

The primary objective is to compare the time to progression (TTP) of three daily doses of thalidomide (100, 200 and 400 mg) with high-dose dexamethasone in relapsed refractory multiple myeloma (MM) patients and to subsequently select the optimum thalidomide dose in terms of median TPP and toxicity.

Conditions

Multiple Myeloma

Keywords

Relapsed Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• The evaluation of Independent Review Committee-documented time to progression (TTP).

  >160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms

Secondary Outcomes (11)

• Response rate (CR + PR), according to the EBMT criteria

  Every 4 weeks

• Response duration

  Every 4 weeks

• Clinical benefit as measured by ECOG performance status, transfusion requirement and Grade ≥3 infections (assessed by the National Cancer Institute Common Toxicity Criteria)

  Every 4 weeks

• Progression-free survival (PFS)

  Disease progression evaluated every 4 weeks

• Overall survival (OS)

  Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms

Study Arms (4)

A

EXPERIMENTAL

Oral thalidomide (100mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

Drug: Thalidomide

B

EXPERIMENTAL

Oral thalidomide (200mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

Drug: Thalidomide

C

EXPERIMENTAL

Oral thalidomide (400mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

Drug: Thalidomide

D

ACTIVE COMPARATOR

High dose oral dexamethasone will be administered at a dose of 40mg/day on days 1-4, 9-12 and 17-20 of each 28-day cycle for cycles 1-4. Beginning with cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg/day on days 1-4 of each 28-day cycle. Dexamethasone will be administered until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

Drug: Dexamethasone

Interventions

Thalidomide DRUG

Oral thalidomide (100mg or 200mg or 400 mg/day) administered to the patient once daily until progression of the disease and for a maximum of 336 + 36 days (12 cycles of 28 +/- 3 days).

A; B; C

Dexamethasone DRUG

High dose oral dexamethasone will be administered at a dose of 40mg/day on days 1-4, 9-12 and 17-20 of each 28-day cycle for cycles 1-4. Beginning with cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg/day on days 1-4 of each 28-day cycle. Dexamethasone will be administered until progression of the disease and for a maximum of 336 +/- 36 days (12 cycles of 28 +/- 3 days).

D

Eligibility Criteria

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

You may qualify if:

• Male or female patients, aged ≥ 18 years at the time of signing the informed consent form
• Patients who have been previously diagnosed with MM who have received between 1 \& 3 prior lines of treatment for their disease, and who require therapy because of disease progression
• Secretory MM with measurable levels of monoclonal protein in serum (\> 10 g/L of IgG M-protein or \> 5 g/L of IgA M-protein) or urine (≥ 200 mg/ 24hours); Patient with the following rare subclasses of the immunoglobulin: IgD, IgE, IgM can be included in the study if the level of monoclonal protein in serum is \> 5g/L or ≥ 200 mg/24hours in urine. As IgM immunoglobulin isotype can be related to Waldenstrom's macroglobulinemia, it is important to distinguish and not include in the study patients with Waldenstrom's macroglobulinemia.
• ECOG performance status of 0, 1, or 2
• Life expectancy \>3months
• Able to adhere to the study visit schedule \& other protocol requirements
• Women of child-bearing potential must agree to use 2 methods of contraception for at least 4weeks before starting the therapy, during the Treatment Period, \& for 4 weeks after the last dose
• Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity during the Treatment Period \& for 4 weeks after the last dose
• Written, informed consent

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the Informed Consent Form
• Pregnant or lactating women. A serum β-hCG pregnancy test must be performed at the Screening visit for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilized women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy)
• Non-secretory MM
• Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) \<500 cells/mm3 (0.5 x 109/L); Platelet count \<30,000/mm3 (30.0 x 109L) without transfusion support within 7 days before the test; Serum creatinine \>3.0mg/dL (265μmol/L); Serum aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) \>3.0 x upper limit of normal (ULN); Serum total bilirubin \>2.0mg/dL (34μmol/L)
• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if s/he were to participate in the study, or which confounds the ability to interpret data from the study
• Severe cardiac dysfunction (according to the New York Heart Association \[NYHA\] classification III-IV)
• Severe bradycardia (\<50bpm)
• Peripheral neuropathy ≥Grade 2 in severity (according to the NCI CTC Version 3.0)
• Prior history of malignancy (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been free of disease for ≥5years
• Patient received any chemotherapy, corticosteroids (\> 10 mg/day prednisone or equivalent as a continuous dose) within 4 weeks before randomization
• Previously treated with thalidomide or thalidomide derivatives
• Patients refractory to high-dose dexamethasone (defined as experiencing less than a PR to dexamethasone, or PD within 6months after discontinuing dexamethasone, or discontinued dexamethasone because of ≥Grade 3 dexamethasone-related toxicity. Previous high-dose dexamethasone therapy is defined as \>500mg dexamethasone or equivalent over a 10week period, whether administered alone or as part of the VAD regimen)
• Contraindications for high-dose dexamethasone
• Active or chronic gastrointestinal ulcers, active viral infections (herpes, varicella, HIV, hepatitis B, hepatitis C), glaucoma, uncontrolled hypertension, or diabetes mellitus, unless well controlled \& under strict supervision during dexamethasone treatment
• Patient enrolled in another clinical trial or who have participated in another trial with the last 4weeks before randomization

Sponsors & Collaborators

• Celgene: lead

Study Sites (86)

Clinic of Haematology, University Multiprofiled Hospital for Active Treatment "G. Stranski"

Pleven, 5800, Bulgaria

Location

Clinic of Haematology, University Multiprofiled Hospital for Active Treatment

Plovdiv, 4002, Bulgaria

Location

University of Multiprofiled Hospital for Active Treatment "Alexandrovska" - Sofia

Sofia, 1431, Bulgaria

Location

Military Medical Academy/Dept Haematology and Oncology

Sofia, 1606, Bulgaria

Location

National Center of Haematology & Transfusiology

Sofia, 1756, Bulgaria

Location

Clinic of Haematology, Multiprofiled Hospital for Active Treatment "Sveta Marina"

Varna, 9010, Bulgaria

Location

Klinicki Bolnicki Centar Rijeka Interna Klinika

Rijeka, 51000, Croatia

Location

Klinika Bolnica SPLIT - Klinika za Unutarnje Bolesti

Split, 21000, Croatia

Location

KBC Zagreb - Klinika za Unutarnje Bolesti

Zagreb, 10000, Croatia

Location

Klinicka Bolnica "Dubrava" Klinika za Unutarnje Bolesti

Zagreb, 10000, Croatia

Location

Klinicka Bolnica "Sestre milosrdnice" Klinika za Unutarnje Bolesti

Zagreb, 10000, Croatia

Location

Klinicka Bolnica MERKUR - Klinika za Unutarnje Bolesti

Zagreb, 10000, Croatia

Location

Interni Hemato-Onkologicka Klinika

Brno, 20 625 00, Czechia

Location

Hematologicka Klinika, Fakultni Nemocnice Hradec Kralove

Hradec Králové, 48 500 05, Czechia

Location

Onkologicke Centrum J.G. Mendela

Novi Jicin, 73601, Czechia

Location

Interni Klinika, Oddeleni Hematoonkologie

Olomouc, 6 775 20, Czechia

Location

Interni Klinika, Oddeleni Hematoonkologie

Prague, 2128 08, Czechia

Location

Hematologicka Klinika, Fakultni Nemocnice Kralovske Vinohrady Srobarova

Prague, 50 100 34, Czechia

Location

CHRU de Lille - Hopital Claude Huriez

Lille, 59037, France

Location

CHU de Nancy - Hopital Brabois

Nancy, 54511, France

Location

Hematologie - CHU Purpan Place du Dr. Baylac

Toulouse, 31059, France

Location

Charite, Universitatsmedizin Berlin, Campus Robert-Rossle Klinik

Berlin, 13125, Germany

Location

Med. Klinik I/University Bonn

Bonn, 53105, Germany

Location

Universitaetsklinik - Klinik fur innere Medizin

Cologne, 50924, Germany

Location

Medizinische Klinik und Poliklinik I/Carl-Gustav-Carus University

Dresden, 01307, Germany

Location

Hematology, Oncology & Clinical Immunology/Heinrich-Heine-University

Düsseldorf, 40225, Germany

Location

Abt. Haematologie - Onkologie/ Allg. Krankenhaus

Hamburg, 22763, Germany

Location

Allgemeinse Krankenhaus St. Georg Hamatologische Abteilung

Hamburg, D-20099, Germany

Location

Medizinische Klinik Abteilung Innere V/Universitatsklinikum

Heidelberg, 69120, Germany

Location

Universitat Schleswig Holstein II Med. Klinik

Kiel, 24116, Germany

Location

Medizinische Klinik und Poliklinik III/Klinikum der Universitaet Muenchen

München, D-81377, Germany

Location

Innere Medizin University Hospital

Münster, 48149, Germany

Location

Abteilung Haematologie - Univeresitaetsklinikum

Saale, D-06120, Germany

Location

Robert-Bosch-Krankenhaus GmbH, Stuttgart

Stuttgart, 70376, Germany

Location

Universitaetsklinik - Abteilung Innere Medizin III

Ulm, 89081, Germany

Location

Med. Klinik II/Klinikum of the Julius-Maximilians-University

Würzburg, 97070, Germany

Location

National Medical Centre Dpt Haematology

Budapest, 351135, Hungary

Location

Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat

Győr, H-9024, Hungary

Location

Pandy Kalman Megyei Korhaz, Megyei Onkologiai Centrum

Gyula, 5700, Hungary

Location

Szent-Gyorgyi Albert University II Clinic of Internal Medicine

Szeged, 6720, Hungary

Location

Nizam's Institute of Medical Sciences, Department of Medical Oncology

Hyderabaad, 500082, India

Location

Department of Medical Oncology, Amrita Institute of Medical Sciences

Kerala, 682 026, India

Location

Orchid Nursing Home

Kolkata, 700054, India

Location

Department of Medical Oncology, Dayanand Medical College DMCH

Ludhiana, 141 001, India

Location

Department of Medical Oncology/Tata Memorial Hospital

Mumbai, 400012, India

Location

Department of Medical Oncology, S.L. Raheja Hospital

Mumbai, 400016, India

Location

Department of Medical Oncology, Jaslok Hospital and Research Centre

Mumbai, 400026, India

Location

Department of Medical Oncology, Deenanath Mangeshkar Hospital

Pune, 411004, India

Location

Department of Medical Oncology/Regional Cancer Centre

Trivandrum, 695 011, India

Location

Instituto di Ematologia e Oncologia Medica

Bologna, 40138, Italy

Location

Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospedaliera S. Giovanni Battista

Torino, 310126, Italy

Location

Department of Internal Medicine - Baguio General Hospital & Medical Center

Baguio City, 2600, Philippines

Location

Chong Hua Hospital

Cebu City, 6000, Philippines

Location

Doctors Clinic Makati Medical Center

Makati City, 1200, Philippines

Location

University of Sto Tomas Hospital

Manila, 1108, Philippines

Location

Doctors Clinic - National Kidney & Transplant Institute

Quezon City, 1100, Philippines

Location

St. Luke's Medical Center

Quezon City, 1102, Philippines

Location

SPSK, Klinika Hematologii Akademii Medycznej

Bialystok, 15-276, Poland

Location

Klinika Hematologii Akademii Medycznej w Gdanskuul

Gdansk, 80-952, Poland

Location

Katedra i Klinika Hematologii i Transplantacji Szpiku - Slaska Akademia Medyczna

Katowice, 40-027, Poland

Location

Swietokrzyskie Centrum Onkologii SPZOZ Poradnia Hematologii

Kielce, 25-734, Poland

Location

Klinika Hematologii Uniwersytetu Medycznego

Lodz, 93-510, Poland

Location

Klinika Chorob Wewnetrznych i Hemagologii

Warsaw, 00-909, Poland

Location

Katedra i Klinika Hematologii, Onkologii I Chorob Wewnetrznych

Warsaw, 02-097, Poland

Location

Instytut Hematologii i Transfuzjologii - Klinika Hematologiczna

Warsaw, 02-776, Poland

Location

Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Klinika Hematologii Nowotworow Krwi i Transplantacji - Szpiku Akademii Medycznej

Wroclaw, 50-367, Poland

Location

Hospital da Universidade de Coimbra - Servico de Hematologia Clinica

Coimbra, 3000-075, Portugal

Location

Instituto Portugues de Oncologia

Lisbon, 1099-023, Portugal

Location

Hospital Geral de Santo Antonio - Servico de Hematologia Clinica

Porto, 4099-001, Portugal

Location

Institute of Hematology, Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Clinic for Hematology, Clinical Centre Nis

Niš, 18000, Serbia

Location

Clinic for Hematology, Clinical Centre Novi Sad

Novisad, 21000, Serbia

Location

Department of Internal Medicine, National Cancer Institute

Bratilslava, 83310, Slovakia

Location

Hematology Department University Hospital

Bratilslava, 85107, Slovakia

Location

Hematology Department, University Hospital PJS

Košice, 04066, Slovakia

Location

University of Free State, Faculty of Health Science, Dept of Hematology & Cell Biology

Bloemfontein, 9301, South Africa

Location

Tygerberg Hospital, University of Stellenbosch, Department of Haematology

Cape Town, 7505, South Africa

Location

Department of Haematology, UCT Medical School

Cape Town, South Africa

Location

Chris Hani Baragwanath Hospital, Clinical Haematology Unit

Johannesburg, 2013, South Africa

Location

Medical Oncology Centre of Rosebank

Johannesburg, 2196, South Africa

Location

Johannesburg Hospital, Department of Medical Oncology

Parktown, 2193, South Africa

Location

Oncology Research Unit Heartlands Hospital

Birmingham, B95 SS, United Kingdom

Location

Clinical Haematology, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Haematology Department - King's College Hospital

London, SE5 9RS, United Kingdom

Location

Department of Haematology-Oncology, The Royal Marsden NHS Foundation Trust

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Kropff M, Baylon HG, Hillengass J, Robak T, Hajek R, Liebisch P, Goranov S, Hulin C, Blade J, Caravita T, Avet-Loiseau H, Moehler TM, Pattou C, Lucy L, Kueenburg E, Glasmacher A, Zerbib R, Facon T. Thalidomide versus dexamethasone for the treatment of relapsed and/or refractory multiple myeloma: results from OPTIMUM, a randomized trial. Haematologica. 2012 May;97(5):784-91. doi: 10.3324/haematol.2011.044271. Epub 2011 Dec 1.

  PMID: 22133776 BACKGROUND

• Kropff M, et al. OPTIMUM Dose of Thalidomide for Relapsed Multiple Myeloma. Presented at American Society of Hematology 2009, New Orleans, LA. Abstract No. 959

  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Thalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Martin Kropff, MD

  Universitatsklinikum Munster

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2007
• First Posted: March 27, 2007
• Study Start: February 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: January 1, 2009
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

HU (4); PT (3); PH (6); CZ (6); SL (3); SE (3); FR (3); CR (6); IT (2); GB (4); PL (10); BU (6); ZA (6); IN (9); DE (15)