A Pilot Study to Establish the Safety & Efficacy of a Combination of Dexamethasone & Lenalidomide in Patients With Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL)
In this study we plan to assess the safety and tolerability of the combination of
dexamethasone, and lenalidomide (D+L) in patients with relapsed or refractory CLL, a
subgroup with limited treatment options. Lenalidomide offers an alternative way of treating
CLL. In a Phase 1 safety and pharmacokinetics study (study 1398/180) in healthy male
volunteers, it was demonstrated that lenalidomide administered at a dose of 100 mg twice a
day for 6 days had an acceptable safety profile with grade 1-2 rash and pruritus being the
primary adverse events associated with the administration of the compound. In myeloma and
MDS, lenalidomide has been studied mostly at two doses: 25 mg/day and 10 mg/day. In CLL
significant toxicity was observed with these two dose levels, including tumour lysis
syndrome and tumour flare.47,48 We therefore plan to start therapy with lenalidomide at a
relatively low dose of 5mg/day, days 1-28, with cycle 1 and escalate to the maximum dose of
10mg/day with cycles 2-12. We have elected to administer lenalidomide continuously as
opposed to pulsing over 14-21 days of each cycle to reduce the risk of tumour flare reaction
(TFR), when this agent is reintroduced with each cycle. Finally, lenalidomide will be
administered in combination with Dexamethasone, at a dose of 20mg/day for 4 days in each 28
day cycle as this allows convenient oral administration. We and others have demonstrated
that Dexamethasone level is effective in CLL patients who are refractory or have relapsed
following primary Fludarabine therapy. The combination of D+L will likely reduce toxicity,
especially TFR, whilst improving overall efficacy without promoting the emergence of
chemoresistant clones in which tumour suppressor genes have been inactivated.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients who achieve objective response (CR + PR) according to the updated 1996 NCIWG criteria measured at 4 weeks after the completion of chemotherapy
4 weeks after the completion of chemotherapy
No
Amit Nathwani
Principal Investigator
University College, London
United Kingdom: Medicines and Healthcare Products Regulatory Agency
UCL/09/387
NCT01459211
May 2012
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