Safety Study of Preimplantation Factor (PIF-1) to Treat Acute Steroid-Resistant Graft-Versus-Host Disease (GVHD)

Phase 1

• Conditions: Graft Vs Host Disease
• Interventions: Drug: Preimplantation factor (PIF-1)

• Registration Number: NCT00517907
• Lead Sponsor: Hadassah Medical Organization

Brief Summary

The primary goal of this study is to determine the safety and tolerability of a novel peptide - preimplantation factor (PIF-1) - in patients who develop acute steroid-resistant graft-versus-host disease (GVHD) after matched bone marrow transplant (BMT).

Following matched BMT, patients will be placed on standard GVHD preventive therapy (cyclosporine); those who do not respond to cyclosporine are placed on a high-dose steroid regimen for 3 days. Patients that do not respond to this standard treatment will be given PIF-1 subcutaneously for 14 days.

Clinical data and samples will be collected, during PIF-1 administration and for an additional three months thereafter, to examine the long-term effect of PIF-1 treatment on the patients' GVHD status.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2007-08-16
• Study First Submitted QC: 2007-08-16
• Study First Posted: 2007-08-17
• Status Verified: 2008-08
• Last Update Submitted: 2015-06-10
• Last Update Posted: 2015-06-11
• Study Start: 2016-01
• Primary Completion: 2018-01
• Study Completion: 2018-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria

• Morbidity unrelated to GVHD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Preimplantation factor (PIF-1)	6 steroid-resistant acute GVHD patients, post-matched BMT (serial)

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of PIF-1 in steroid-resistant patients who develop acute GVHD, as evidenced by clinical and laboratory indices	within 90 days after first PIF-1 injection

Secondary Outcome Measures

Name	Time	Method
Therapeutic effect of PIF-1 on participants' acute GVHD status, as determined by comparison with the clinical and laboratory indices before intervention	within 90 days after first PIF-1 injection

Trial Locations

Locations (1)

Hadassah Medical Organization; 🇮🇱 Jerusalem, Israel