Opening of 'Gleevec+IL2' phase 1 trial at Gustave Roussy

By Estelle Lecointe
President, Association Française des Patients du GIST: Ensemble conte le GIST

After several years of research and months of expectation, Professor Laurence Zitvogel’s research team at the Gustave Roussy Institute in France finally got the agreement from the AFSSAPS (The French Health Products Safety Agency) and the support from Novartis to launch a phase I clinical trial called “IMAIL-2” combining “Gleevec + Interleukine 2” .

This clinical trial has two major objectives:

• Assessing the efficacy of the chemical “Gleevec+IL2” combination in the treatment of various cancers, including GIST.

• Identifying the existence of IKDC cells in the human body.

Brief reminder about IKDCs:

IKDCs (Interferon Killer Dendritic Cells) are cells of the immune system which are naturally produced by mice bodies and located in the bone marrow, liver, spleen and ganglions. Their peculiarity lies in their capacity to kill cancer cells.

Several tests conducted on mice, allowed Professor Zitvogel’s team to highlight that, when IKDCs are numerous and stimulated, they spontaneously move to the tumor cells and reduce them to nothingness in a few hours. This is thanks to the large amount of interferon gamma (IFN-y) and complex lyse systems (perforine/granzyme, TRAIL) they naturally secrete or secrete after a stimulation. Unfortunately, IKDCs are very rare and therefore have an extremely limited natural effect on tumors.

Considering this, the “IMAIL-2” clinical trial is aiming at assessing if the “Gleevec+IL2” combination can:

• Contribute to increase the secretion of interferon gamma in the human body so as to boost the immune system and make it more potent to fight against tumor cells.

• Stimulate the production of IKDCs and increase their activity within the human body.

Eligibility:

• Primary or secondary Gleevec resistance; progressive disease on Sutent

• No brain metastasis

• Good liver and kidneys functions

Number of GIST patients expected to be included: 4 or 5 minimum.

Progress of the clinical trial:

One week of Gleevec (400mg/day) plus one week of Gleevec and IL2, then one week off. The duration, as well as the number of cycles will depend on the clinical response.

Pre-treatment:

Three weeks prior to the beginning of the “Gleevec+IL2” treatment, patients will be prescribed “cyclophosphamide” pills (Endoxan) they will have to take every day during this period. The aim of this pre-treatment is to regulate the activation of the Treg cells and thus to stimulate the production of NK and IKDC cells. This pre-treatment does not imply any side-effect.

Expecting dosages:

• Three levels of dosage escalation are expected (gradually up to nine million of IU/M2/day, three times a week).

• There will be no dosage escalation concerning Gleevec which will be maintained at 400mg/day during the entire study.

In case of progression during trial:

Only the dosage of interleukine 2 will be increased. Gleevec will always be maintained at 400mg/day. In case of complete remission: The discontinuation or the continuation of the treatment is still a debate. The only thing known is that there won’t be any randomization as it doesn’t exist in phase I clinical trials. A phase II clinical trial is planned to be opened as soon as the dosage/efficacy ratio is determined in 2009.

For more information, please contact: Dr. Nathalie Chaput, Nathalie.chaput@igr.fr, +33(0)1 42 11 50 05.