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

Chronic Lymphocytic Leukemia Clinical Trial

— LLC0606  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00727415
• Other study ID #: LLC0606
• Secondary ID: LLC06062006-0061
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2008
• Est. completion date: January 2016

Study information

• Verified date: August 2018
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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).
• 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).
• 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.

Locations

Country	Name	City	State
Italy	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	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	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	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	U.O.C. Ematologia - Ospedale S.Eugenio	Rome
Italy	Universita Degli Studi "La Sapeinza"	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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.	After 6 months from study entry (end of treatment)
Secondary	Toxicity as Assessed by NCI CTCAE v3.0	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)
Secondary	Number of Patients With Severe Infections	Severe infection requiring more than 2 weeks of antibiotic therapy.	At 24 months from study entry (end of follow-up)
Secondary	Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).		After 6 months from study entry (end of treatment).

External Links

•   GIMEMA Foundation Website