Trial Information

Phase I Clinical Trial to Assess Safety of Synthetic Preimplantation Factor (PIF-1) in Patients With Steroid-Resistant Acute Graft-Versus-Host Disease (GVHD) After Allogeneic Hematopoietic Stem-Cell Transplantation

Allogeneic BMT is a well-established treatment modality for malignant and non-malignant
hematological diseases. Mature donor T cells within the stem-cell graft are the main
mediators of the beneficial immune effects, but they are also responsible for the induction
of GVHD, which becomes the major cause of morbidity and mortality post-transplant. Acute
GVHD occurs within a 100-day period post-transplant and generally is manifested by
dermatitis, enteritis, and hepatitis. The treatment of GVHD continues to be a challenge. To
eliminate undesirable host-derived hematopoietic elements before BMT, patients are
traditionally treated with myeloablative conditioning regimens involving high-dose
chemotherapy and total-body irradiation. Standard GVHD prophylaxis and therapy comprise
drugs that cause generalized immune suppression and place patients in danger of
opportunistic infections and tumor relapse. For acute GVHD prevention, cyclosporine is often
used; however, it is frequently necessary to administer long-term high-dose steroids as
well.

An acute GVHD patient's lack of response to steroids is associated with poor prognosis. The
ideal prophylaxis treatment for BMT patients would be one that prevented the graft from
attacking the host, and that modulated the host's immune response so that it would accept
the transplant, while maintaining its ability to protect the body against opportunistic
hostile agents.

Pregnancy is an immune paradox: it allows maternal (host) acceptance of a semi-allograft
(embryo), while it does not cause graft-versus-host or host-versus-graft reactions against
the host/mother, or immune suppression. Therefore, the pregnant immunological status is
compatible with the desired immune profile in patients undergoing BMT. By replicating the
immune profile present in pregnancy in BMT patients, we may be able to reduce the occurrence
of GVHD-related morbidity and mortality rates.

Preimplantation factor (PIF-1) is a novel, embryo-secreted peptide whose synthetic version
matches the native peptide's properties. PIF-1 appears to play an important role in
mediating the maternal response to pregnancy in mammals. In preclinical studies, PIF-1 has
been found to be effective in preclinical BMT-GVHD models, without apparent toxicity.