Lenalidomide, Fludarabine & Cyclophosphamide in Advanced Chronic Lymphocytic Leukemia Not Responding to Therapy (LLC0606)

August 10, 2018 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

A Prospective Multicenter Pilot Trial to Evaluate the Efficacy of a Treatment With Fludarabine, Cyclophosphamide, Lenalidomide (FCL) for Advanced Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) Patients.

This is a phase I - II multicenter, non-comparative, open label study in patients with previously treated CLL aimed at defining the MTD of Lenalidomide given in combination with Fludarabine, Cyclophosphamide and at evaluating the (CR) rate of FC given in combination with the MTD of Lenalidomide (FCL).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To define the maximum tolerated dose (MTD) of Lenalidomide given in combination with FC.(Phase I)
  • To evaluate the complete remission (CR) rate of FC given in combination with the MTD of Lenalidomide (FCL). (Phase II)

Secondary

  • To define the toxicity and the infection rate of patients treated with FCL and the median number of delivered courses of FCL, overall response rate and the progression-free survival and the relationship between the response and the baseline biologic factors (IgVH, FISH, ZAP-70, CD38).
  • To evaluate the overall response rate (complete and partial responses).
  • To evaluate the progression-free survival.

OUTLINE: This is a phase I - II multicenter, non-comparative, open label study in patients with previously treated CLL aimed at defining the MTD of Lenalidomide given in combination with Fludarabine, Cyclophosphamide and at evaluating the (CR) rate of FC given in combination with the MTD of Lenalidomide (FCL).

All patients will receive six monthly courses of FCL schedule consisting of three days of Fludarabine and Cyclophosphamide administration (d1-d3) combined with 14 days of Lenalidomide administration (d1-d14).

After completion of study treatment, patients are followed periodically for up to 18 months.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bari, Italy, 70010
        • Unità Operativa Ematologia 1 - Università degli Studi di Bari
      • Bologna, Italy
        • Istituto di Ematologia e Oncologia Medica "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
      • Catanzaro, Italy, 88100
        • Azienda Ospedaliera Pugliese Ciaccio
      • Ferrara, Italy, 44100
        • Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
      • Genova, Italy
        • Clinica Ematologica - Università degli Studi
      • Latina, Italy
        • Divisione di Ematologia Ospedale "Santa Maria Goretti"
      • Meldola, Italy
        • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
      • Messina, Italy
        • Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
      • Milano, Italy
        • UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
      • Nocera Inferiore, Italy
        • (SA) U.O. di Oncoematologia di Nocera Inferiore-plesso ospedaliero "A. Tortora" di Pagani del DEA Nocera-Pagani
      • Padova, Italy
        • Università degli Studi di Padova - Ematologia ed Immunologia Clinica
      • Pescara, Italy
        • U.O. Ematologia Clinica - Azienda USL di Pescara
      • Piacenza, Italy
        • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
      • Ravenna, Italy, I-48100
        • Ospedale S. M. delle Croci
      • Reggio Calabria, Italy, 89100
        • Azienda Ospedaliera Bianchi Melacrino Morelli
      • Rimini, Italy
        • Ospedale "Infermi"
      • Roma, Italy
        • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
      • Rome, Italy, 00161
        • Universita Degli Studi "La Sapeinza"
      • Rome, Italy, 00168
        • Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
      • Rome, Italy
        • U.O.C. Ematologia - Ospedale S.Eugenio
      • Siena, Italy, 53100
        • U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
      • Terni, Italy
        • SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
      • Udine, Italy
        • Clinica Ematologica - Policlinico Universitario

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Age >=18 years.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Patients with advanced stage or progressive CLL (NCI criteria) and relapsed or refractory disease.
  • No more than 2 previous different treatment lines.
  • No treatment with Campath-1H in the previous 6 months.
  • Disease-free of prior malignancies for >=5 years, with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • All previous cancer therapy, including chemotherapy, immunotherapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
  • ECOG performance status of <=2 at study entry.

  • 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
  • Able to take low molecular weight heparin or in alternative, low- fixed-dose warfarin or, in alternative, low-dose aspirin.
  • Able to understand and voluntarily sign the informed consent form.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10 - 14 days prior to therapy and repeated within 24 hours of starting study. FCBP must agree to use two reliable forms of contraception for at least 28 days before starting study drug; while participating in the study; and for at least 4 weeks after discontinuation from the study.
  • Females must agree to abstain from breastfeeding during study participation and for at least 28 days after discontinuation from the study.
  • Males must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 4 weeks following discontinuation.
  • (Other details regarding pregnancy tests and contraception are reported in the chapter "Eligibility Criteria" within the study protocol).

Exclusion criteria:

  • Treatment with Campath-1H during the previous 6 months.
  • Concurrent use of other anti-cancer agents.
  • Positive DAT with clinical and laboratory signs of hemolysis, autoimmune thrombocytopenia.
  • Known positivity for HIV or active infectious hepatitis.
  • Active bacterial, viral, or fungal infection requiring systemic anti-viral, antibiotic or anti-fungal therapy.
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or breast feeding females (lactating females must agree not to breast feed while taking Lenalidomide).
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Prior history or presence of thrombosis, thromboembolism, hearth failure or arrhythmia, neurologic disease and renal insufficiency.
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • Known hypersensitivity to thalidomide.
  • The development of erythema nodosum, desquamating rash while taking thalidomide or similar drugs.
  • Any prior use of Lenalidomide
  • Lactose intolerance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose of Lenalidomide (Phase I)
Time Frame: The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.
Maximum tolerated dose of lenalidomide given in combination with fludarabine.
The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.
Overall Complete Response (CR) Rate (Phase II)
Time Frame: After 6 months from study entry (end of treatment).
Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular.
After 6 months from study entry (end of treatment).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Reaching Disease-free Survival (DSF) Overall
Time Frame: After 6 months from study entry (end of treatment)
Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular.
After 6 months from study entry (end of treatment)
Toxicity as Assessed by NCI CTCAE v3.0
Time Frame: At 24 months from study entry (end of follow-up)
Data from all subjects who receive any study drug will be included in the safety analyses.
At 24 months from study entry (end of follow-up)
Number of Patients With Severe Infections
Time Frame: At 24 months from study entry (end of follow-up)
Severe infection requiring more than 2 weeks of antibiotic therapy.
At 24 months from study entry (end of follow-up)
Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).
Time Frame: After 6 months from study entry (end of treatment).
After 6 months from study entry (end of treatment).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

August 1, 2008

First Submitted That Met QC Criteria

August 1, 2008

First Posted (Estimate)

August 4, 2008

Study Record Updates

Last Update Posted (Actual)

January 22, 2019

Last Update Submitted That Met QC Criteria

August 10, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLC0606 (Other Identifier: GIMEMA)
  • 2006-006185-42 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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