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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00910910
First received: May 28, 2009
Last updated: July 8, 2014
Last verified: July 2014
  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 AND SAFETY OF LENALIDOMIDE (REVLIMID®) VERSUS CHLORAMBUCIL AS FIRST-LINE THERAPY FOR PREVIOUSLY UNTREATED ELDERLY PATIENTS WITH B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Resource links provided by NLM:


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 ]
    Number of participants who survive without progressing

  • Safety [type, frequency, and severity of adverse events (AEs)] [ Time Frame: Up to 105 months; every 28 days ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a patient during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairmentof the patient's health, including laboratory test values (as specified by the criteria below), regardless of etiology. Any medical condition that was present prior to study treatment and that remains unchanged or improved should not be recorded as an AE. If there is a worsening of thatmedical condition, this should be considered an AE.

  • Overall Survival [ Time Frame: Up to 105 months ] [ Designated as safety issue: No ]
    Overall Survival is defined as the time between randomization and death

  • Number of anti-cancer therapies obtained from randomized participants [ Time Frame: Up to 105 months ] [ Designated as safety issue: No ]
    Anti-cancer therapies administered to all randomized study participants during the follow up period


Secondary Outcome Measures:
  • Response, including evaluation of minimal residual disease (MRD) by flow cytometry (Hallek, 2008) [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
    Response, including evaluation of minimal residual disease (MRD), will be assessed by IWCLL guidelines for diagnosis and treatment of CLL. The response rate based on the best response during the treatment period and the relative proportions in each response category will be examined.

  • Duration of response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
    Duration of response is defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression and is determined

  • Time to response [ Time Frame: Every 28 days ] [ Designated as safety issue: No ]
    Time to response is calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines

  • 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 ]
    FACT-Leukemia is a validated cancer quality of life measure used to evaluate patients receiving cancer treatment.


Enrollment: 450
Study Start Date: November 2009
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (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

Detailed Description:

After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the number of deaths in patients treated with lenalidomide versus patients treated with chlorambucil. No specific causality for this imbalance has been identified to date. Investigators were instructed to immediately discontinue all participants from experimental lenalidomide treatment and inform their patients accordingly. Participants on the Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant completing in March 2014. All randomized participants will continue to be followed for overall survival and secondary primary malignancies.

  Eligibility

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

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

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]
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 166 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Oliver Kong, MD Celgene Corporation
  More Information

Additional Information:
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: July 8, 2014
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 Pública 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, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lenalidomide
Thalidomide
Chlorambucil
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014