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Chlorambucil + Lenalidomide and Lenalidomide Maintenance in Untreated Elderly With Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT01403246
Recruitment Status : Terminated (Slow patient enrollment and new molecules for chronic lymphoid leukemia, have importantly reduced the interest of conducting the phase II of this study.)
First Posted : July 27, 2011
Results First Posted : January 23, 2019
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Tracking Information
First Submitted Date  ICMJE January 13, 2011
First Posted Date  ICMJE July 27, 2011
Results First Submitted Date  ICMJE February 23, 2016
Results First Posted Date  ICMJE January 23, 2019
Last Update Posted Date February 12, 2019
Study Start Date  ICMJE November 2011
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2019)
Number of Dose Limiting Toxic Events (DLT) of Lenalidomide Given in Combination With Chlorambucil. [ Time Frame: At maximum 8 months from induction therapy start ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2011)
PhI: MTD [ Time Frame: At maximum 8 months from induction therapy start ]
PhI: MTD will be identified according to all adverse events and DLTs tabulated for each dose level.
Change History Complete list of historical versions of study NCT01403246 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2011)
  • Lenalidomide and chlorambucil induction therapy in terms of safety; [ Time Frame: After 20 months therapy and 18-60 months follow-up ]
    Induction phase with chlorambucil and Lenalidomide in terms of safety [type, frequency, and severity of adverse events (AEs)].
  • Post-remissional phase with Lenalidomide in terms of safety [ Time Frame: After 20 months therapy and 18-60 months follow-up ]
    type, frequency, and severity of adverse events (AEs)
  • Lenalidomide maintenance efficacy in terms of CR rate. [ Time Frame: After 20 months therapy and 18-60 months follow-up ]
  • Progression free survival estimation according to the post-remissional approach. [ Time Frame: After 20 months therapy and 18-60 months follow-up starting from date of randomization in the maintenance therapy. ]
  • Association between the response and the baseline biologic factors (IgVH, p53, FISH, ZAP-70, CD38) [ Time Frame: After 20 months therapy and 18-60 months follow-up ]
  • Progression free survival estimation according to the baseline biologic factors starting from the date of first dose of study drug in the induction phase. [ Time Frame: After 20 months therapy and 18-60 months follow-up ]
  • Time to a new CLL treatment or death estimation. [ Time Frame: an estimation of 40 months. ]
  • Overall survival estimation [ Time Frame: an estimation of 40 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chlorambucil + Lenalidomide and Lenalidomide Maintenance in Untreated Elderly With Chronic Lymphocytic Leukemia (CLL)
Official Title  ICMJE Phase I-II Multicenter Study to Assess the Efficacy and Safety of the Chlorambucil + Lenalidomide Combination and Lenalidomide Maintenance Therapy in Untreated Elderly Pts With CLL. EudraCT Number 2009-013415-35
Brief Summary This is a phase I multicenter, open label study in previously untreated and elderly patients (> 60 years) with CLL: a non-comparative phase aimed at defining the MTD of lenalidomide given in combination with chlorambucil and the efficacy and safety of the lenalidomide and chlorambucil combination.
Detailed Description

All patients will receive six monthly courses of the chlorambucil (C) and lenalidomide (L) schedule consisting of 8 days of C (d1-d8) combined with L given daily until response assessment which will take place 12 weeks from the start (d+1) of course VI, while patients continue their treatment with lenalidomide daily.

In the first phase of the induction phase of the study the dose of L given with C will be gradually escalated to reach the MTD.

Patients who will achieve a response after 6 courses of CL induction phase -PR, CRi, CR

The study was first designed to be a phase I-II trial, yet the second phase of the study was not conducted due to different reasons, among which: poor accrual and lack of interest.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: Lenalidomide; Chlorambucil
MTD of lenalidomide given in combination with chlorambucil
Study Arms  ICMJE Experimental: Lenalidomide with Chlorambucil
Intervention: Drug: Lenalidomide; Chlorambucil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 27, 2015)
9
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2011)
81
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • CLL diagnosis according to the 2008 revised NCI criteria.
  • Age > 65 years or between 60 and 65 years if not suitable for fludarabine-based regimens according to the investigator's judgment.
  • ECOG performance status of ≤2 at study entry.
  • No previous treatment.
  • Advanced stage or progressive CLL according to the 2008 revised NCI criteria.
  • Disease-free of prior malignancies other than CLL for ≥3 years, with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • Able to take low molecular weight heparin or in alternative, low-fixed-dose warfarin or, in alternative, low-dose aspirin.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Female subjects of childbearing potential(FCBP) must:

    • Understands the potential teratogenic risk to the unborn child and the need for effective contraception;
    • Be capable of complying with effective contraceptive measures.
    • Be informed and understand the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
    • Understand the need to commence the study treatment as soon as study drug is dispensed following a negative pregnancy test.
    • Uderstand the need and accepts to undergo pregnancy testing based on the frequency outlined in this protocol.
    • Contraception.
    • Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation.
    • The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
    • Highly effective methods:

      1. Intrauterine device (IUD)
      2. Hormonal (birth control pills, injections, implants)
      3. Tubal ligation
      4. Partner's vasectomy
    • Additional effective methods:

      1. Male condom
      2. Diaphragm
      3. Cervical Cap
  • Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended. If a patient is currently using combined oral contraception the patient should switch to one of the effective method listed above. The risk of venous thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.
  • Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia.
  • Pregnancy testing.
  • FCBP must have two negative pregnancy tests prior to starting study drug. The first pregnancy test must be performed within 10 to 14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug.
  • FCBP must agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
  • Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug discontinuation.
  • Male patients must:

    • Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a female of childbearing potential.
    • Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
    • If pregnancy or a positive pregnancy test does occur in the partner of a male study patient during study participation, the investigator must be notified immediately.
  • Female and male patients:

    • should be instructed never to give this medicinal product to another person and to return any unused capsules to the study doctor at the end of treatment.
    • Should not donate blood during therapy and for at least 28 days following discontinuation of study drug.
    • Male patients should not donate blood, semen or sperm during therapy or for at least 28 days following discontinuation of study drug.
  • Laboratory test results within these ranges:

    • Serum creatinine ≤1.5 mg/dL and creatinine clearance ≥ 60mL/min
    • Total bilirubin ≤1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) ≤1.5 x ULN.
  • All patients must be able to understand and voluntarily sign the informed consent form.

Exclusion criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • A CIRS score > 6.
  • Pregnant or Lactating Females.
  • Known positive serology for HIV or active hepatitis B or C.
  • Active infection requiring systemic anti-viral, antibiotic or anti-fungal therapy.
  • History of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months.
  • History of renal failure requiring dialysis.
  • Known presence of alcohol and/or drug abuse.
  • History of thrombosis, thromboembolism within one year.
  • Hearth failure, arrhythmia.
  • ≥ grade 2 neuropathy.
  • Uncontrolled hyperthyroidism or hypothyroidism.
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
  • One or more laboratory abnormalities:
  • calculated creatinine clearance (Cockroft-Gault) <60mL/min;
  • electrolyte abnormalities according to the Cairo Bishop definition of laboratory TLS.
  • GOT, GPT, γGT > 1.5 x upper limit of normal value;
  • serum bilirubin >1.5 mg/dL.
  • Lactose Intolerance.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01403246
Other Study ID Numbers  ICMJE CLL0709
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gruppo Italiano Malattie EMatologiche dell'Adulto
Study Sponsor  ICMJE Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Roberto Foà Umberto I - Dipartimento di Biotecnologie Cellulari ed Ematologia Cellulari
Principal Investigator: Francesca Romana Mauro, Co-Coordinator Umberto I - Dipartimento di Biotecnologie Cellulari ed Ematologia
PRS Account Gruppo Italiano Malattie EMatologiche dell'Adulto
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP