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Chronic Lymphocytic LeukemiaPhase 1/2LLC0606NCT00727415

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

A Phase 1/2 study testing Cyclophosphamide, Fludarabine phosphate and Lenalidomide in people with Chronic Lymphocytic Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 23 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Cyclophosphamide, Fludarabine phosphate and Lenalidomide
How many people
42 participants
Where
23 sitesItaly
Study dates
Feb 2008to Jan 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

Italy23 sites

  • Unità Operativa Ematologia 1 - Università degli Studi di Bari

    Bari, 70010

  • Istituto di Ematologia e Oncologia Medica "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

    Bologna

  • Azienda Ospedaliera Pugliese Ciaccio

    Catanzaro, 88100

  • Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

    Ferrara, 44100

  • Clinica Ematologica - Università degli Studi

    Genova

  • Divisione di Ematologia Ospedale "Santa Maria Goretti"

    Latina

  • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

    Meldola

  • Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"

    Messina

  • UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

    Milan

  • (SA) U.O. di Oncoematologia di Nocera Inferiore-plesso ospedaliero "A. Tortora" di Pagani del DEA Nocera-Pagani

    Nocera Inferiore

  • Università degli Studi di Padova - Ematologia ed Immunologia Clinica

    Padova

  • U.O. Ematologia Clinica - Azienda USL di Pescara

    Pescara

  • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

    Piacenza

  • Ospedale S. M. delle Croci

    Ravenna, I-48100

  • Azienda Ospedaliera Bianchi Melacrino Morelli

    Reggio Calabria, 89100

  • Ospedale "Infermi"

    Rimini

  • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

    Roma

  • Universita Degli Studi "La Sapeinza"

    Rome, 00161

  • Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

    Rome, 00168

  • U.O.C. Ematologia - Ospedale S.Eugenio

    Rome

  • U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

    Siena, 53100

  • SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni

    Terni

  • Clinica Ematologica - Policlinico Universitario

    Udine

Other trials in Italy

About this study

Official title: 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).

Read the 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.

Keywords
advanced or progressive chronic lymphocytic leukemia, Lenalidomide, Fludarabine
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    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).

  • Fludarabine phosphateDrug

    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).

  • LenalidomideDrug

    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).

    In the first phase of the study, the dose of Lenalidomide given with FC will be gradually escalated to reach the MTD. In the second phase of the study, FC will be given in combination with the Lenalidomide escalated to the MTD or the maximum planned dose.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose of Lenalidomide (Phase I)

    Maximum tolerated dose of lenalidomide given in combination with fludarabine.

    Measured: The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.

  2. Overall Complete Response (CR) Rate (Phase II)

    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.

    Measured: After 6 months from study entry (end of treatment).

Secondary outcomes (4)

  1. Number of Patients Reaching Disease-free Survival (DSF) Overall

    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.

    Measured: After 6 months from study entry (end of treatment)

  2. Toxicity as Assessed by NCI CTCAE v3.0

    Data from all subjects who receive any study drug will be included in the safety analyses.

    Measured: At 24 months from study entry (end of follow-up)

  3. Number of Patients With Severe Infections

    Severe infection requiring more than 2 weeks of antibiotic therapy.

    Measured: At 24 months from study entry (end of follow-up)

  4. Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).

    Measured: After 6 months from study entry (end of treatment).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2008 (estimated)
  2. Study startFeb 2008
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00727415
Sponsor's protocol ID
LLC0606
Other IDs
LLC0606, 2006-006185-42
Acronym
LLC0606
Status last verified
Aug 2018
First submitted
1 Aug 2008
Last updated
22 Jan 2019
Data monitoring committee
No
Individual data sharing
No

Publications

  • Mauro FR, Carella AM, Molica S, Paoloni F, Liberati AM, Zaja F, Belsito V, Cortellezzi A, Rizzi R, Tosi P, Spriano M, Ferretti A, Nanni M, Marinelli M, De Propris MS, Orlando SM, Vignetti M, Cuneo A, Guarini AR, Foa R. Fludarabine, cyclophosphamide and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA trial. Leuk Lymphoma. 2017 Jul;58(7):1640-1647. doi: 10.1080/10428194.2016.1258698. Epub 2016 Nov 23.

    PubMed 27881039

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Fludarabine phosphate and Lenalidomide in people with Chronic Lymphocytic Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 23 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00727415, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.

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