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

NCT ID: NCT00727415

Last Updated: 2019-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2016-01-31

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).

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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).

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Foa, MD

Role: PRINCIPAL_INVESTIGATOR

Universita Degli Studi "La Sapeinza"

Locations

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, , 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, , Italy

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

Ferrara, , 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, , Italy

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, , 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, , Italy

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

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

Rome, , Italy

U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

Siena, , 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

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 27881039 (View on PubMed)

Related Links

http://www.gimema.it

GIMEMA Foundation Website

Other Identifiers

LLC0606

Identifier Type: OTHER

Identifier Source: secondary_id

2006-006185-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LLC0606

Identifier Type: -

Identifier Source: org_study_id