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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT00452569

Collaborator

(none)

499

Enrollment

Locations

Arms

Actual Duration (Months)

5.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Thalidomide Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

499 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2006

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Jan 1, 2009

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
Composite of disease progression and death (recurrent time(s) from randomisation to disease progression and/or death) [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) [Baseline/Week 8/ Week 16/Week 24/Week 32/Week 40/Week 48]
Adverse events (AEs) [Every 4 weeks]
Assessment of peripheral neuropathy [Screening, Week 24, Week 48]
Vital signs and physical examination [Every 4 weeks]
Clinical laboratory tests [Every 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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