Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial) - Full Text View

Purpose

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.

Condition	Intervention	Phase
B-Cell Chronic Lymphocytic Leukemia (B-CLL)	Drug: Lenalidomide Drug: Chlorambucil	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 3, Multicenter, Randomized, Open-Label, Parallel-Group Study Of The Efficacy & Safety Of Lenalidomide (Revlimid®) Vs. Chlorambucil As First-Line Therapy For Previously Untreated Elderly Patients With B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Chlorambucil Lenalidomide

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Progression Free Survival (PFS) [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [type, frequency, and severity of adverse events (AEs)] [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
Response, including evaluation of minimal residual disease (MRD) by flow cytometry (Hallek, 2008) [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
Duration of response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
Time to response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
Overall survival (OS) [ Time Frame: Three times a year ] [ Designated as safety issue: No ]
Health-Related Quality of Life (HRQL) by Functional Assessment of Cancer Therapy -Leukemia (FACT-Leu) and EQ-5D [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

Enrollment:	450
Study Start Date:	May 2009
Estimated Study Completion Date:	February 2018
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 - Lenalidomide 1 - Lenalidomide	Drug: 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. Other Name: Revlimid
Active Comparator: 2- Chlorambucil 2- Chlorambucil	Drug: 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). Other Name: Leukeran

Arms

Assigned Interventions

Experimental: 1 - Lenalidomide

1 - Lenalidomide

Drug: 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.

Other Name: Revlimid

Active Comparator: 2- Chlorambucil

2- Chlorambucil

Drug: 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).

Other Name: Leukeran

Detailed Description:

CC-5013-CLL-008 is a Phase 3, multi-center, randomized, open-label, parallel-group study that will compare the efficacy and safety of oral lenalidomide to that of oral chlorambucil in elderly patients with previously untreated B-cell CLL. Eligible patients must not have received any treatment for their B-cell CLL, must be symptomatic, and must be ≥ 65 years of age.

Eligibility

Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Must sign an informed consent form.
Age ≥ 65 years
Must be able to adhere to the study visit schedule and other protocol requirements.
Must have a documented diagnosis of B-cell CLL.
Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
Must agree to follow pregnancy precautions as required by the protocol.
Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
Must agree not to donate blood or semen as defined by the protocol

Exclusion Criteria:

Prior treatment for B-cell CLL.
Any medical condition, that would prevent the subject from signing the informed consent form.
Active infections requiring systemic antibiotics.
Systemic infection that has not resolved > 2 months prior to initiating lenalidomide
Pregnant or lactating females.
Participation in any clinical study or having taken any investigational therapy within 28 days.
Known presence of alcohol and/or drug abuse.
Central nervous system (CNS) involvement.
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)
History of renal failure requiring dialysis.
Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
Prior therapy with lenalidomide.
Evidence of TLS at screening
Presence of specific hematology and/or chemistry abnormalities
Uncontrolled hyperthyroidism or hypothyroidism
Venous thromboembolism within one year
≥ Grade-2 neuropathy
Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910910

Show 153 Study Locations

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Oliver Kong, MD

Celgene Corporation

More Information

Additional Information:

Click here for more information about this study This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00910910 History of Changes
Other Study ID Numbers:	CC-5013-CLL-008, 2008-003079-32
Study First Received:	May 28, 2009
Last Updated:	May 16, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: National Health Surveillance Agency Chile: Instituto de Salud Publica de Chile Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Austria: Agency for Health and Food Safety Belgium: Federal Agency for Medicinal Products and Health Products Bulgaria: Bulgarian Drug Agency Croatia: Agency for Medicinal Product and Medical Devices Czech Republic: State Institute for Drug Control Denmark: Danish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Hungary: National Institute of Pharmacy Italy: The Italian Medicines Agency Netherlands: Medicines Evaluation Board (MEB) Norway: Norwegian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Romania: National Medicines Agency Russia: Ministry of Health of the Russian Federation Serbia and Montenegro: Agency for Drugs and Medicinal Devices Slovakia: State Institute for Drug Control Spain: Spanish Agency of Medicines United Kingdom: Medicines and Healthcare Products Regulatory Agency Israel: Ministry of Health South Africa: Medicines Control Council Australia: Department of Health and Ageing Therapeutic Goods Administration New Zealand: Medsafe

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Chlorambucil
Lenalidomide
Thalidomide
Antineoplastic Agents, Alkylating
Alkylating Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013