Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00910910




Registration number
NCT00910910
Ethics application status
Date submitted
28/05/2009
Date registered
1/06/2009
Date last updated
9/07/2019

Titles & IDs
Public title
Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)
Scientific title
A Phase 3, Multicenter, Randomized, Openlabel, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) Versus Chlorambucil as First-Line Therapy for Previously Untreated Elderly Patients With B-Cell Chronic Lymphocytic Leukemia (The Origin Trial)
Secondary ID [1] 0 0
2008-003079-32
Secondary ID [2] 0 0
CC-5013-CLL-008
Universal Trial Number (UTN)
Trial acronym
ORIGIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-Cell Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Chlorambucil

Experimental: 1 - Lenalidomide - 1 - Lenalidomide

Active comparator: 2- Chlorambucil - 2- Chlorambucil


Treatment: Drugs: Lenalidomide
For patients with normal renal function (defined as CrCl = 60 mL/min), 5 mg once daily on Days 1 through 28 of the first 28-day cycle, 10 mg once daily on Days 1 through 28 starting at the second cycle, 15 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.

For patients with moderate renal impairment (defined as CrCl = 30 to \< 60 mL/min), 2.5 mg once daily on Days 1 through 28 of the first 28-day cycle, 5 mg once daily on Days 1 through 28 starting at the second cycle, 7.5 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.

Treatment: Drugs: Chlorambucil
Patients assigned to the chlorambucil arm will receive oral chlorambucil tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan-Meier Estimate of Progression Free Survival (PFS)
Timepoint [1] 0 0
From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
Primary outcome [2] 0 0
Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014
Timepoint [2] 0 0
From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
Secondary outcome [1] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [1] 0 0
From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil
Secondary outcome [2] 0 0
Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014
Timepoint [2] 0 0
From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil
Secondary outcome [3] 0 0
Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
Timepoint [3] 0 0
Up to data cut-off date of 18 Feb 2013; approximately 39 months
Secondary outcome [4] 0 0
Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014
Timepoint [4] 0 0
Up to data cut-off of 31 March 2014; approximately 53 months
Secondary outcome [5] 0 0
Kaplan-Meier Estimate for Duration of Response
Timepoint [5] 0 0
Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Secondary outcome [6] 0 0
Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014
Timepoint [6] 0 0
Up to data cut-off of 31 March 2014; up to approximately 53 months
Secondary outcome [7] 0 0
Time to Response
Timepoint [7] 0 0
Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Secondary outcome [8] 0 0
Time to Response for a Later Cut-off Date of 31 March 2014
Timepoint [8] 0 0
Up to data cut-off of 31 March 2014; up to approximately 53 months
Secondary outcome [9] 0 0
Kaplan Meier Estimate of Overall Survival
Timepoint [9] 0 0
Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months
Secondary outcome [10] 0 0
Kaplan Meier Estimate for Overall Survival at the Final Analysis
Timepoint [10] 0 0
Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Secondary outcome [11] 0 0
Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument
Timepoint [11] 0 0
Day 1 and once every 8 weeks
Secondary outcome [12] 0 0
Euro Quality of Life Five Dimension (EQ-5D) Questionnaire
Timepoint [12] 0 0
Day 1 and once every 8 weeks
Secondary outcome [13] 0 0
Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment
Timepoint [13] 0 0
Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months

Eligibility
Key inclusion criteria
1. Must sign an informed consent form.
2. Age = 65 years
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Must have a documented diagnosis of B-cell CLL.
5. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of =2.
6. Must agree to follow pregnancy precautions as required by the protocol.
7. Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
8. Must agree not to donate blood or semen as defined by the protocol
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment for B-cell CLL.
2. Any medical condition, that would prevent the subject from signing the informed consent form.
3. Active infections requiring systemic antibiotics.
4. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide
5. Pregnant or lactating females.
6. Participation in any clinical study or having taken any investigational therapy within 28 days.
7. Known presence of alcohol and/or drug abuse.
8. Central nervous system (CNS) involvement.
9. Prior history of malignancies, other than CLL, unless the subject has been free of the disease for =3 years. Exceptions include the following:

* Basal cell carcinoma of the skin
* Squamous cell carcinoma of the skin
* Carcinoma in situ of the cervix
* Carcinoma in situ of the breast
* Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
10. History of renal failure requiring dialysis.
11. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
12. Prior therapy with lenalidomide.
13. Evidence of TLS at screening
14. Presence of specific hematology and/or chemistry abnormalities
15. Uncontrolled hyperthyroidism or hypothyroidism
16. Venous thromboembolism within one year
17. = Grade-2 neuropathy
18. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
19. Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2018
Sample size
Target
Accrual to date
Final
450
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
IMVS - Adelaide
Recruitment hospital [3] 0 0
Western Hospital - Footscray
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
St. Vincent Hospital - Fitzroy
Recruitment hospital [7] 0 0
Nepean Hospital - Kingswood, NSW
Recruitment hospital [8] 0 0
Calvary Mater Hospital - Waratah
Recruitment hospital [9] 0 0
Westmead Hospital Australia - Westmead
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
2751 - Kingswood, NSW
Recruitment postcode(s) [8] 0 0
2298 - Waratah
Recruitment postcode(s) [9] 0 0
NSW2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Austria
State/province [17] 0 0
Innsbruck
Country [18] 0 0
Austria
State/province [18] 0 0
Vienna
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Belgium
State/province [20] 0 0
Haine-Saint Paul
Country [21] 0 0
Belgium
State/province [21] 0 0
Kortrijk
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
Yvoir
Country [24] 0 0
Brazil
State/province [24] 0 0
Bahia
Country [25] 0 0
Brazil
State/province [25] 0 0
Minas Gerais
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio Grande Do Sul
Country [27] 0 0
Brazil
State/province [27] 0 0
São Paulo
Country [28] 0 0
Brazil
State/province [28] 0 0
Brasílía
Country [29] 0 0
Brazil
State/province [29] 0 0
Curitiba
Country [30] 0 0
Brazil
State/province [30] 0 0
Londrina
Country [31] 0 0
Brazil
State/province [31] 0 0
Morumbi
Country [32] 0 0
Brazil
State/province [32] 0 0
Rio de Janeiro
Country [33] 0 0
Brazil
State/province [33] 0 0
Santo Andre
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Pleven
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Plovdiv
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Sofia
Country [37] 0 0
Bulgaria
State/province [37] 0 0
Varna
Country [38] 0 0
Canada
State/province [38] 0 0
New Brunswick
Country [39] 0 0
Canada
State/province [39] 0 0
Newfoundland and Labrador
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Chile
State/province [41] 0 0
Renaca
Country [42] 0 0
Chile
State/province [42] 0 0
Temuco
Country [43] 0 0
Colombia
State/province [43] 0 0
Monteria
Country [44] 0 0
Croatia
State/province [44] 0 0
Split
Country [45] 0 0
Croatia
State/province [45] 0 0
Zagreb
Country [46] 0 0
Czechia
State/province [46] 0 0
Hradec Kralove
Country [47] 0 0
Czechia
State/province [47] 0 0
Ostrava
Country [48] 0 0
Czechia
State/province [48] 0 0
Prague
Country [49] 0 0
Denmark
State/province [49] 0 0
Copenhagen
Country [50] 0 0
Denmark
State/province [50] 0 0
Harlev
Country [51] 0 0
Denmark
State/province [51] 0 0
Roskilde
Country [52] 0 0
France
State/province [52] 0 0
Bordeaux
Country [53] 0 0
France
State/province [53] 0 0
Grenoble cedex 09
Country [54] 0 0
France
State/province [54] 0 0
Limoges
Country [55] 0 0
France
State/province [55] 0 0
Nice
Country [56] 0 0
France
State/province [56] 0 0
Strasbourg
Country [57] 0 0
Hungary
State/province [57] 0 0
Debrecen
Country [58] 0 0
Hungary
State/province [58] 0 0
Kaposvar
Country [59] 0 0
Hungary
State/province [59] 0 0
Szeged
Country [60] 0 0
Hungary
State/province [60] 0 0
Tatabanya
Country [61] 0 0
Hungary
State/province [61] 0 0
Vasvari Pal U. 2
Country [62] 0 0
Israel
State/province [62] 0 0
Afula
Country [63] 0 0
Israel
State/province [63] 0 0
Ashkelon
Country [64] 0 0
Israel
State/province [64] 0 0
Beer Sheva
Country [65] 0 0
Israel
State/province [65] 0 0
Haifa
Country [66] 0 0
Israel
State/province [66] 0 0
Jerusalem
Country [67] 0 0
Israel
State/province [67] 0 0
Kfar-Saba
Country [68] 0 0
Israel
State/province [68] 0 0
Naharia
Country [69] 0 0
Israel
State/province [69] 0 0
Petach Tikva
Country [70] 0 0
Israel
State/province [70] 0 0
Rehovot
Country [71] 0 0
Israel
State/province [71] 0 0
Tel Aviv
Country [72] 0 0
Israel
State/province [72] 0 0
Tel Hashomer
Country [73] 0 0
Italy
State/province [73] 0 0
Bari
Country [74] 0 0
Italy
State/province [74] 0 0
Firenze
Country [75] 0 0
Italy
State/province [75] 0 0
Milan
Country [76] 0 0
Italy
State/province [76] 0 0
Modena
Country [77] 0 0
Italy
State/province [77] 0 0
Naples
Country [78] 0 0
Italy
State/province [78] 0 0
Novara
Country [79] 0 0
Italy
State/province [79] 0 0
Orbassano
Country [80] 0 0
Italy
State/province [80] 0 0
Padova
Country [81] 0 0
Italy
State/province [81] 0 0
Pisa
Country [82] 0 0
Italy
State/province [82] 0 0
Potenza
Country [83] 0 0
Italy
State/province [83] 0 0
Siena
Country [84] 0 0
Italy
State/province [84] 0 0
Torrette Di Ancona
Country [85] 0 0
Netherlands
State/province [85] 0 0
Eindhoven
Country [86] 0 0
Netherlands
State/province [86] 0 0
Hoofddorp
Country [87] 0 0
Netherlands
State/province [87] 0 0
Zwolle
Country [88] 0 0
New Zealand
State/province [88] 0 0
Christchurch
Country [89] 0 0
New Zealand
State/province [89] 0 0
Takapuna
Country [90] 0 0
Poland
State/province [90] 0 0
Gdansk
Country [91] 0 0
Poland
State/province [91] 0 0
Lodz
Country [92] 0 0
Poland
State/province [92] 0 0
Torun
Country [93] 0 0
Poland
State/province [93] 0 0
Warszawa
Country [94] 0 0
Poland
State/province [94] 0 0
Wroclaw
Country [95] 0 0
Portugal
State/province [95] 0 0
Coimbra
Country [96] 0 0
Portugal
State/province [96] 0 0
Porto
Country [97] 0 0
Romania
State/province [97] 0 0
Bucharest
Country [98] 0 0
Romania
State/province [98] 0 0
Iasi
Country [99] 0 0
Romania
State/province [99] 0 0
Sibiu
Country [100] 0 0
Romania
State/province [100] 0 0
Timisoara
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Arkhangelsk
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Barnaul
Country [103] 0 0
Russian Federation
State/province [103] 0 0
Ekaterinburg
Country [104] 0 0
Russian Federation
State/province [104] 0 0
Moscow
Country [105] 0 0
Russian Federation
State/province [105] 0 0
Nizhniy Novgorod
Country [106] 0 0
Russian Federation
State/province [106] 0 0
Novosibirsk
Country [107] 0 0
Russian Federation
State/province [107] 0 0
St. Petersburg
Country [108] 0 0
Serbia
State/province [108] 0 0
Kragujevac
Country [109] 0 0
Serbia
State/province [109] 0 0
Nis
Country [110] 0 0
Slovakia
State/province [110] 0 0
Bratislava
Country [111] 0 0
Slovakia
State/province [111] 0 0
Martin
Country [112] 0 0
South Africa
State/province [112] 0 0
Parktown
Country [113] 0 0
South Africa
State/province [113] 0 0
Pretoria
Country [114] 0 0
Spain
State/province [114] 0 0
Badalona
Country [115] 0 0
Spain
State/province [115] 0 0
Barcelona
Country [116] 0 0
Spain
State/province [116] 0 0
Madrid
Country [117] 0 0
Spain
State/province [117] 0 0
Majadahonda
Country [118] 0 0
Spain
State/province [118] 0 0
Murcia
Country [119] 0 0
Spain
State/province [119] 0 0
Salamanca
Country [120] 0 0
Spain
State/province [120] 0 0
San Sebastian
Country [121] 0 0
Spain
State/province [121] 0 0
Santander
Country [122] 0 0
Spain
State/province [122] 0 0
Valencia
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Bournemouth
Country [124] 0 0
United Kingdom
State/province [124] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and efficacy of lenalidomide as a first line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will compare the effects (good and bad) of lenalidomide with chlorambucil.
Trial website
https://clinicaltrials.gov/study/NCT00910910
Trial related presentations / publications
Chanan-Khan A, Egyed M, Robak T, Martinelli de Oliveira FA, Echeveste MA, Dolan S, Desjardins P, Blonski JZ, Mei J, Golany N, Zhang J, Gribben JG. Randomized phase 3 study of lenalidomide versus chlorambucil as first-line therapy for older patients with chronic lymphocytic leukemia (the ORIGIN trial). Leukemia. 2017 May;31(5):1240-1243. doi: 10.1038/leu.2017.47. Epub 2017 Jan 31. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Jeffrey Jones, MD
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00910910