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Lenalidomide, Fludarabine, and Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia That Did Not Respond to Previous Therapy (LLC0606)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00727415
First received: August 1, 2008
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Cyclophosphamide
Drug: Fludarabine phosphate
Drug: Lenalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose of lenalidomide given in combination with fludarabine.

  • Overall complete response (CR) rate (Phase II) [ Time Frame: After 6 months from study entry (end of treatment). ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • CR rate (Phase I) [ Time Frame: After 6 months from study entry (end of treatment) ] [ Designated as safety issue: No ]
    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.

  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: At 24 months from study entry (end of follow-up) ] [ Designated as safety issue: Yes ]
    Data from all subjects who receive any study drug will be included in the safety analyses.

  • Infection rate [ Time Frame: At 24 months from study entry (end of follow-up) ] [ Designated as safety issue: Yes ]
    Severe infection requiring more than 2 weeks of antibiotic therapy.

  • Median number of delivered courses of treatment. [ Time Frame: After 6 months from study entry (end of therapy). ] [ Designated as safety issue: No ]
  • Overall response rate. [ Time Frame: After 6 months from study entry (end of treatment). ] [ Designated as safety issue: No ]
  • Progression-free survival. [ Time Frame: After 24 months from study entry (end of follow-up). ] [ Designated as safety issue: No ]
  • Correlation between response and baseline biologic parameters (i.e., IgVH, FISH, ZAP-70, CD38). [ Time Frame: After 6 months from study entry (end of treatment). ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: February 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cyclophosphamide
    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).
    Drug: Fludarabine phosphate
    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).
    Drug: Lenalidomide

    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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00727415

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

Additional Information:
No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT00727415     History of Changes
Other Study ID Numbers: LLC0606, GIMEMA-LLC0606, EUDRACT-2006-006185-42
Study First Received: August 1, 2008
Last Updated: January 30, 2014
Health Authority: Italy: Ethics Committee
Italy: Ministry of Health

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
advanced or progressive chronic lymphocytic leukemia
Lenalidomide
Fludarabine

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Lenalidomide
Thalidomide
Vidarabine
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Growth Inhibitors
Growth Substances
Immunologic Factors

ClinicalTrials.gov processed this record on November 25, 2014