CompletedPhase 2ACTRN12608000404325

An Australian, phase II , multicentre, randomised, open-label, dose intensification study of three patient cohorts, investigating varying dose schedules, each of 6 x 28day cycles, with monitoring continuing for 12 months into the post treatment period.

An Australian, phase II , multicentre, randomised, dose intensification study investigating oral fludarabine, oral cyclophosphamide, and intravenous rituximab (poFCivR) tolerance in previously untreated elderly (=65years old) patients with chronic lymphocytic leukaemia. (CLL)

Sponsor

Australasian Leukaemia and Lymphoma Group

Enrollment

120 participants

Start Date

Dec 10, 2008

Study Type

Interventional

Conditions

Chronic Lymphocytic Leukaemia (CLL)

Summary

The trial is a randomised phase II open-label multicentre trial investigating oral fludarabine, cyclophosphamide and intravenous rituximab in previously untreated elderly (= 65 years old) patients with chronic lymphocytic leukaemia. The primary objective is to investigate the tolerability of each of three of these combination chemotherapies and the associated primary endpoint is the proportion of paitens able to complete 6 cycles of therapy.

Eligibility

Sex: Both males and femalesMin Age: 65 Yearss

Inclusion Criteria14

B-CLL confirmed according to National Cancer Institute (NCI) Working Group Criteria.
Binet stage B or C, or progressive symptomatic stage A (see Protocol Appendix I).
Age = 65 years old.
Judged to be in need of systemic therapy (see Protocol Appendix II).
No previous treatment (chemotherapy, radiotherapy or immunotherapy) for CLL.
Alkaline phosphatase and transaminases = 2 x ULN.(Upper Limits of Normal)
Creatinine clearance = 50 ml/min (as calculated by (estimated Glomerular Filtration Rate) eGFR; eGFR also calculated by
Cockcroft and Gault formula for final analysis; see Protocol Appendix III).
Females of childbearing potential or fertile males must take contraceptive measures during
and at least 6 months after cessation of therapy.
(Eastern Cooperative Group) ECOG performance status 0-1.
Cumulative Illnes Rating Scale CIRS score < 6 (see Protocol Appendix IV).
Life expectancy > 6 months.
Patient’s written informed consent.

Exclusion Criteria25

Age < 65 years old.
Non-progressive or stable Binet stage A.
Clinically significant auto-immune cytopenia, Coombs-positive haemolytic anaemia (as
discerned by treating physician).
Active second malignancy currently requiring treatment (except for non-melanoma skin
cancer or cervical cancer in situ or tumour treated curatively by surgery > 5 years ago)
Concomitant disease requiring prolonged use of glucocorticoids (> 1 month).
Known hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or
any of the study drugs.
ECOG performance status 2-3.
Class III or IV cardiac disease defined by the NYHA.
Severe or debilitating pulmonary disease.
Severe or debilitating central nervous system disease or cerebral dysfunction.
Transformation to aggressive B-cell malignancy, e.g. diffuse large cell lymphoma, Richter’s
syndrome or prolymphocytic leukaemia.
Active bacterial, viral or fungal infection; patients who have known Human Immunodeficiency
Virus (HIV) infection or active hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection.
Total bilirubin > 2 x ULN.
Creatinine clearance < 50 ml/min (as calculated by eGFR).
Any coexisting medical or psychological condition that would preclude participation in the
required study procedures.
Treatment with any other investigational agent, or participation in another clinical trial
within 30 days prior to entering this study.
Pregnancy and lactation.

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Interventions

To investigate the safety and tolerability of fludarabine, cyclophosphamide, and rituximab in previously untreated elderly (=65years old) patients with chronic lymphocytic leukaemia. (CLL). Treatm

To investigate the safety and tolerability of fludarabine, cyclophosphamide, and rituximab in previously untreated elderly (=65years old) patients with chronic lymphocytic leukaemia. (CLL). Treatment Arm1:oral fludarabine 24 mg/m2 days 1-5. plus intravenous (i.v.) rituximab Cycle 1: 375 mg/m2 day 0* Cycles 2-6: 500 mg/m2 day 1 (Fludarabine Rituximab:FR5), Treatment Arm2 and Arm3 :oral fludarabine 24 mg/m2 days 1-3. plus oral cyclophosphamide 150 mg/m2 days 1-3. in varing dose intensity with i.v. rituximab Cycle 1: 375 mg/m2 day 0* Cycles 2-6: 500 mg/m2 day 1 (Fludarabine Cyclophosphamide Rituximab: FCR3 and Fludarabine Cyclophosphamide Rituximab FCR 5). Dose schedule is determined via randomisation. Duration is x6 28day cycles. There is no wash out period between cycles.