Lenalidomide, Fludarabine & Cyclophosphamide in Advanced Chronic Lymphocytic Leukemia Not Responding to Therapy
LLC0606
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.
2 other identifiers
interventional
42
1 country
23
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2008
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2008
CompletedFirst Submitted
Initial submission to the registry
August 1, 2008
CompletedFirst Posted
Study publicly available on registry
August 4, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedResults Posted
Study results publicly available
January 22, 2019
CompletedJanuary 22, 2019
August 1, 2018
7.9 years
August 1, 2008
November 8, 2017
August 10, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose of Lenalidomide (Phase I)
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)
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 Outcomes (4)
Number of Patients Reaching Disease-free Survival (DSF) Overall
After 6 months from study entry (end of treatment)
Toxicity as Assessed by NCI CTCAE v3.0
At 24 months from study entry (end of follow-up)
Number of Patients With Severe Infections
At 24 months from study entry (end of follow-up)
Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).
After 6 months from study entry (end of treatment).
Interventions
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).
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).
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.
Eligibility Criteria
You may qualify if:
- 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.
- +3 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Unità Operativa Ematologia 1 - Università degli Studi di Bari
Bari, 70010, Italy
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, 88100, Italy
Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
Ferrara, 44100, Italy
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
Milan, 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
Padua, 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, I-48100, Italy
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Calabria, 89100, Italy
Ospedale "Infermi"
Rimini, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma, Italy
Universita Degli Studi "La Sapeinza"
Rome, 00161, Italy
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, 00168, Italy
U.O.C. Ematologia - Ospedale S.Eugenio
Rome, Italy
U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
Siena, 53100, Italy
SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
Terni, Italy
Clinica Ematologica - Policlinico Universitario
Udine, Italy
Related Publications (1)
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.
PMID: 27881039DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Alfonso Piciocchi
- Organization
- GIMEMA
Study Officials
- PRINCIPAL INVESTIGATOR
Roberto Foa, MD
Universita Degli Studi "La Sapeinza"
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 1, 2008
First Posted
August 4, 2008
Study Start
February 1, 2008
Primary Completion
January 1, 2016
Study Completion
January 1, 2016
Last Updated
January 22, 2019
Results First Posted
January 22, 2019
Record last verified: 2018-08
Data Sharing
- IPD Sharing
- Will not share