Trial Information

A Phase I Study of Haematopoietic Stem Cell Mobilization Using G-CSF With ATRA in Patients With Cutaneous Lymphoma and Multiple Myeloma

HSPC mobilization is normally achieved using cytokines such as G-CSF, or occasionally
GM-CSF, often in combination with myelosuppressive chemotherapy.

Studies in the mouse model have shown that retinoids (vitamin A derivatives) can be combined
with G-CSF, and that this combination synergizes to enhance HSPC mobilization over that seen
with G-CSF alone.

This trial aims to assess the safety and mobilization efficacy of combining mobilizing doses
of G-CSF with a standard dose of ATRA, using a treatment regimen derived from the earlier
murine studies.

In this phase I pilot study, six patients with multiple myeloma or cutaneous lymphoma will
be treated with ATRA plus G-CSF, and safety and toxicity data collected for the two week
study drug period plus a further two weeks' follow-up. The primary endpoint is safety and
toxicity, the secondary endpoint is an observation of the mobilization efficacy as
demonstrated by CD34+ cell counts over the study period. Patients will not undergo stem cell
collection during this study, as this is purely an observational study. Participating
patients will not be those who would normally be scheduled for stem cell collection and
transplantation in the near future, but rather patients with stable disease who are not
candidates for imminent transplantation, or who have collected adequate HSPC on previous
mobilization attempts and are currently being observed.

Cutaneous lymphoma and multiple myeloma are chosen as suitable disease states for this study
as there is in vitro evidence of a possible disease benefit of retinoids in these disorders.
If disease response is noted during the study or follow up period, ongoing ATRA will be
offered at the discretion of the treating physician.