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

November 14, 2019 updated by: Celgene

Randomised, Controlled, Open-labelled, Multi-centre Comparison of Thalidomide Versus High-dose Dexamethasone for the Treatment of Relapsed Refractory Multiple Myeloma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

499

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Clinic of Haematology, University Multiprofiled Hospital for Active Treatment "G. Stranski"
      • Plovdiv, Bulgaria, 4002
        • Clinic of Haematology, University Multiprofiled Hospital for Active Treatment
      • Sofia, Bulgaria, 1431
        • University of Multiprofiled Hospital for Active Treatment "Alexandrovska" - Sofia
      • Sofia, Bulgaria, 1606
        • Military Medical Academy/Dept Haematology and Oncology
      • Sofia, Bulgaria, 1756
        • National Center of Haematology & Transfusiology
      • Varna, Bulgaria, 9010
        • Clinic of Haematology, Multiprofiled Hospital for Active Treatment "Sveta Marina"
  • Croatia
      • Rijeka, Croatia, 51000
        • Klinicki Bolnicki Centar Rijeka Interna Klinika
      • Split, Croatia, 21000
        • Klinika Bolnica SPLIT - Klinika za Unutarnje Bolesti
      • Zagreb, Croatia, 10000
        • KBC Zagreb - Klinika za Unutarnje Bolesti
      • Zagreb, Croatia, 10000
        • Klinicka Bolnica "Dubrava" Klinika za Unutarnje Bolesti
      • Zagreb, Croatia, 10000
        • Klinicka Bolnica "Sestre milosrdnice" Klinika za Unutarnje Bolesti
      • Zagreb, Croatia, 10000
        • Klinicka Bolnica MERKUR - Klinika za Unutarnje Bolesti
  • Czechia
      • Brno, Czechia, 20 625 00
        • Interni Hemato-Onkologicka Klinika
      • Hradec Kralove, Czechia, 48 500 05
        • Hematologicka Klinika, Fakultni Nemocnice Hradec Kralove
      • Novi Jicin, Czechia, 73601
        • Onkologicke Centrum J.G. Mendela
      • Olomouc, Czechia, 6 775 20
        • Interni Klinika, Oddeleni Hematoonkologie
      • Prague 10, Czechia, 50 100 34
        • Hematologicka Klinika, Fakultni Nemocnice Kralovske Vinohrady Srobarova
      • Prague 2, Czechia, 2128 08
        • Interni Klinika, Oddeleni Hematoonkologie
  • France
      • Lille, France, 59037
        • Chru De Lille - Hopital Claude Huriez
      • Nancy Cedex, France, 54511
        • CHU de Nancy - Hôpital Brabois
      • Toulouse, France, 31059
        • Hematologie - CHU Purpan Place du Dr. Baylac
  • Germany
      • Berlin, Germany, 13125
        • Charite, Universitatsmedizin Berlin, Campus Robert-Rossle Klinik
      • Bonn, Germany, 53105
        • Med. Klinik I/University Bonn
      • Dresden, Germany, 01307
        • Medizinische Klinik und Poliklinik I/Carl-Gustav-Carus University
      • Duesseldorf, Germany, 40225
        • Hematology, Oncology & Clinical Immunology/Heinrich-Heine-University
      • Hamburg, Germany, 22763
        • Abt. Haematologie - Onkologie/ Allg. Krankenhaus
      • Hamburg, Germany, D-20099
        • Allgemeinse Krankenhaus St. Georg Hamatologische Abteilung
      • Heidelberg, Germany, 69120
        • Medizinische Klinik Abteilung Innere V/Universitatsklinikum
      • Kiel, Germany, 24116
        • Universitat Schleswig Holstein II Med. Klinik
      • Koeln, Germany, 50924
        • Universitaetsklinik - Klinik fur innere Medizin
      • Muenchen, Germany, D-81377
        • Medizinische Klinik und Poliklinik III/Klinikum der Universitaet Muenchen
      • Muenster, Germany, 48149
        • Innere Medizin University Hospital
      • Saale, Germany, D-06120
        • Abteilung Haematologie - Univeresitaetsklinikum
      • Stuttgart, Germany, 70376
        • Robert-Bosch-Krankenhaus GmbH, Stuttgart
      • Ulm, Germany, 89081
        • Universitaetsklinik - Abteilung Innere Medizin III
      • Wuerzburg, Germany, 97070
        • Med. Klinik II/Klinikum of the Julius-Maximilians-University
  • Hungary
      • Budapest, Hungary, 351135
        • National Medical Centre Dpt Haematology
      • Gyor, Hungary, H-9024
        • Petz Aladar Megyei Oktato Korhaz, II. Belgyogyaszat
      • Gyula, Hungary, 5700
        • Pandy Kalman Megyei Korhaz, Megyei Onkologiai Centrum
      • Szeged, Hungary, 6720
        • Szent-Gyorgyi Albert University II Clinic of Internal Medicine
  • India
      • Hyderabaad, India, 500082
        • Nizam's Institute of Medical Sciences, Department of Medical Oncology
      • Kerala, India, 682 026
        • Department of Medical Oncology, Amrita Institute of Medical Sciences
      • Kolkata, India, 700054
        • Orchid Nursing Home
      • Ludhiana, India, 141 001
        • Department of Medical Oncology, Dayanand Medical College DMCH
      • Mumbai, India, 400012
        • Department of Medical Oncology/Tata Memorial Hospital
      • Mumbai, India, 400016
        • Department of Medical Oncology, S.L. Raheja Hospital
      • Mumbai, India, 400026
        • Department of Medical Oncology, Jaslok Hospital and Research Centre
      • Pune, India, 411004
        • Department of Medical Oncology, Deenanath Mangeshkar Hospital
      • Trivandrum, India, 695 011
        • Department of Medical Oncology/Regional Cancer Centre
  • Italy
      • Bologna, Italy, 40138
        • Instituto di Ematologia e Oncologia Medica
      • Torino, Italy, 310126
        • Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospedaliera S. Giovanni Battista
  • Philippines
      • Baguio City, Philippines, 2600
        • Department of Internal Medicine - Baguio General Hospital & Medical Center
      • Cebu City, Philippines, 6000
        • Chong Hua Hospital
      • Makati City, Philippines, 1200
        • Doctors Clinic Makati Medical Center
      • Manila City, Philippines, 1108
        • University of Sto Tomas Hospital
      • Quezon City, Philippines, 1102
        • St. Luke's Medical Center
      • Quezon City, Philippines, 1100
        • Doctors Clinic - National Kidney & Transplant Institute
  • Poland
      • Bialystok, Poland, 15-276
        • SPSK, Klinika Hematologii Akademii Medycznej
      • Gdansk, Poland, 80-952
        • Klinika Hematologii Akademii Medycznej w Gdanskuul
      • Katowice, Poland, 40-027
        • Katedra i Klinika Hematologii i Transplantacji Szpiku - Slaska Akademia Medyczna
      • Kielce, Poland, 25-734
        • Swietokrzyskie Centrum Onkologii SPZOZ Poradnia Hematologii
      • Lodz, Poland, 93-510
        • Klinika Hematologii Uniwersytetu Medycznego
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
      • Warszawa, Poland, 00-909
        • Klinika Chorob Wewnetrznych i Hemagologii
      • Warszawa, Poland, 02-097
        • Katedra i Klinika Hematologii, Onkologii I Chorob Wewnetrznych
      • Warszawa, Poland, 02-776
        • Instytut Hematologii i Transfuzjologii - Klinika Hematologiczna
      • Wroclaw, Poland, 50-367
        • Klinika Hematologii Nowotworow Krwi i Transplantacji - Szpiku Akademii Medycznej
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Hospital da Universidade de Coimbra - Servico de Hematologia Clinica
      • Lisboa, Portugal, 1099-023
        • Instituto Portugues de Oncologia
      • Porto, Portugal, 4099-001
        • Hospital Geral de Santo Antonio - Servico de Hematologia Clinica
  • Serbia
      • Belgrade, Serbia, 11000
        • Institute of Hematology, Clinical Centre of Serbia
      • Nis, Serbia, 18000
        • Clinic for Hematology, Clinical Centre Nis
      • Novisad, Serbia, 21000
        • Clinic for Hematology, Clinical Centre Novi Sad
  • Slovakia
      • Bratilslava, Slovakia, 83310
        • Department of Internal Medicine, National Cancer Institute
      • Bratilslava, Slovakia, 85107
        • Hematology Department University Hospital
      • Kosice, Slovakia, 04066
        • Hematology Department, University Hospital PJS
  • South Africa
      • Bloemfontein, South Africa, 9301
        • University of Free State, Faculty of Health Science, Dept of Hematology & Cell Biology
      • Cape Town, South Africa, 7505
        • Tygerberg Hospital, University of Stellenbosch, Department of Haematology
      • Cape Town, South Africa
        • Department of Haematology, UCT Medical School
      • Johannesburg, South Africa, 2196
        • Medical Oncology Centre of Rosebank
      • Johannesburg, South Africa, 2013
        • Chris Hani Baragwanath Hospital, Clinical Haematology Unit
      • Parktown, South Africa, 2193
        • Johannesburg Hospital, Department of Medical Oncology
  • United Kingdom
      • Birmingham, United Kingdom, B95 SS
        • Oncology Research Unit Heartlands Hospital
      • London, United Kingdom, SE1 9RT
        • Clinical Haematology, Guy's Hospital
      • London, United Kingdom, SE5 9RS
        • Haematology Department - King's College Hospital
      • Surrey, United Kingdom, SM2 5PT
        • Department of Haematology-Oncology, The Royal Marsden NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
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
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).
Experimental: B
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
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).
Experimental: C
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
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).
Active Comparator: D
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
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The evaluation of Independent Review Committee-documented time to progression (TTP).
Time Frame: >160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms
>160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms

Secondary Outcome Measures

Outcome Measure
Time Frame
Response rate (CR + PR), according to the EBMT criteria
Time Frame: Every 4 weeks
Every 4 weeks
Response duration
Time Frame: Every 4 weeks
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)
Time Frame: Every 4 weeks
Every 4 weeks
Progression-free survival (PFS)
Time Frame: Disease progression evaluated every 4 weeks
Disease progression evaluated every 4 weeks
Overall survival (OS)
Time Frame: Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms
Evaluated after 150 deaths occurring in Dexamethasone and Thalidomide 400 mg arms
Composite of disease progression and death (recurrent time(s) from randomisation to disease progression and/or death)
Time Frame: Evaluated after 160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms
Evaluated after 160 "IRC confirmed" disease progression in the Dexamethasone or Thalidomide 400 mg/day arms
Quality of life as determined by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)
Time Frame: Baseline/Week 8/ Week 16/Week 24/Week 32/Week 40/Week 48
Baseline/Week 8/ Week 16/Week 24/Week 32/Week 40/Week 48
Adverse events (AEs)
Time Frame: Every 4 weeks
Every 4 weeks
Assessment of peripheral neuropathy
Time Frame: Screening, Week 24, Week 48
Screening, Week 24, Week 48
Vital signs and physical examination
Time Frame: Every 4 weeks
Every 4 weeks
Clinical laboratory tests
Time Frame: Every 4 weeks
Every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Principal Investigator: Martin Kropff, MD, Universitätsklinikum Münster

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2006

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

March 23, 2007

First Submitted That Met QC Criteria

March 26, 2007

First Posted (Estimate)

March 27, 2007

Study Record Updates

Last Update Posted (Actual)

November 18, 2019

Last Update Submitted That Met QC Criteria

November 14, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • THA PH INT 2005 CL001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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