Although I wasn't well enough to attend the last Clinical Trials meeting of the UK CLL sub-group I did receive the agenda. I was impressed by the full portfolio of trials that are available for almost all categories of patients. Here is the list:
As first line treatments:
For patients considered fit for FCR there are two randomized Phase 2 trials:
ADMIRE compares FCR with FCR plus mitoxantrone and ARCTIC compares FCR with FCM plus low dose rituximab.
For patients considered unfit for FCR The current trial, having completed a phase 2 trial of chlorambucil plus rituximab, which will be reported at ASH, is CLL7 which compares chlorambucil plus or minus ofatumumab in a randomized phase 2. After this there is RiAltO which compares chlorambucil + ofaftumumab with bendamustine + ofaftumumab. NB in the chlorambucil trials the chlorambucil is given at 70mg/sq m/month.
As consolidation therapy following first line treatment, we have already completed CLL207 and we move on to CLL8 or CLARET which compares alemtuzumab consolidation with observation.
For poor risk stage A patients who would otherwise be on watch and wait there is RESPECT, which offers Revlimid in a phase 2 study.
For good risk stage A patients, based on the finding of stereotypy, CLEAR is a trial of broad spectrum antibiotics and Helicobacter elimination as a phase 2 study.
For Richter's transformation we Have a phase 2 study of CHOP + Ofatumumab.
For relapsed disease that is not refractory FC v FCO is planned.
For refractory disease or del 17p CLL210 is a phase 2 study of alemtuzumab + revlimid + dexamethasone.
For del 11q we have PiCLLe using the new PARP inhibitor (this study also includes T-PLL and mantle cell lymphoma).
The result of the Chlorambucil + rituximab trial showed an overall response rate of 82% (compared to 66% for chlorambucil in LRF CLL4 which had rather younger and fitter patients). Median progression free survival was 23.5 months - 16% better than the matched CLL4 subset.
Results from CLL207, also to be presented at ASH. 47 patients were entered and they hadhad a median of 2 prior treatments. Alemtuzumab consolidation has a bas name following the CALGB trial. In this study alemtuzumab was give between 6 and 24 months after completing induction therapy with a fludarabine based treatment. The alemtuzumab was given at a dose of 30mg sc for 6 weeks and those who were MRD positive who had shown at least a log reduction in tumor load were continued for a further 6 weeks. There were 2 treatment related deaths (1 EBV lymphoproliferative disease, 1 parainfluenza). 45% showed reactivation of CMV, but all were successfully treated pre-emptively.
Prior to alemtuzumab 24 were in CR and 23 in PR. 13 PRs converted to CR. At the end of the alemtuzumab, 39/47 (83%) had MRD negative bone marrows. 6 months later 48% of the MRD negative patients had become positive 41% remained negative. 6 months later 8/9 were still negative.
It seems that the gratest benefit is to those who become MRD negative at 6 weeks.
A rather strange trial has been adopted. This is a novel supportive care treatment called RaBaP which will be randomized against best supportive care.The drugs are Bezafibrate and medroxyprogesteraone acetate. It is suggested that these agents will stimulate bone marrow.
The final ASH abstract concerns alemtuzumab in refractory disease. We know that about half of refractory patients have del 17p and tend to respond well to alemtuzumab, but what about the non-del 17p cases. The answer is they also do well on alemtuzumab.