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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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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United States of America
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Connecticut
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United States of America
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Illinois
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Indiana
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Kentucky
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Minnesota
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Missouri
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Nevada
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New Jersey
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New York
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Ohio
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Pennsylvania
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South Carolina
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Texas
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Washington
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Wisconsin
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Austria
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Innsbruck
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Austria
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Vienna
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Belgium
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Brussels
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Belgium
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Haine-Saint Paul
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Belgium
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Kortrijk
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Belgium
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Leuven
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Belgium
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Yvoir
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Brazil
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Bahia
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Londrina
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Morumbi
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Pleven
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Zwolle
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Novosibirsk
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St. Petersburg
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Serbia
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Kragujevac
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Serbia
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Nis
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Slovakia
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Bratislava
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Martin
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Parktown
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Pretoria
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Badalona
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Murcia
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Valencia
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Bournemouth
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United Kingdom
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London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Chanan-Khan A, Egyed M, Robak T, Martinelli de Oli... [More Details]