Safety Study of Preimplantation Factor (PIF-1) to Treat Acute Steroid-Resistant Graft-Versus-Host Disease (GVHD) (PIF1GVHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00517907
Recruitment Status : Unknown
Verified August 2008 by Hadassah Medical Organization.
Recruitment status was:  Not yet recruiting
First Posted : August 17, 2007
Last Update Posted : June 11, 2015
BioIncept LLC
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Graft Vs Host Disease Drug: Preimplantation factor (PIF-1) Phase 1

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2016
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2018

Arm Intervention/treatment
Experimental: 1
6 steroid-resistant acute GVHD patients, post-matched BMT (serial)
Drug: Preimplantation factor (PIF-1)

The study will include 6 patients and will last for at least six months. The first three patients will receive PIF-1 (0.5 mg/kg/day for 14 days) by subcutaneous injection. The dosage in the next three patients may be increased to 1 mg/kg/day for 14 days.

Patients will be treated serially: each patient will be followed for 2 weeks after cessation of PIF-1 administration before the next patient begins PIF-1 administration.

Primary Outcome Measures :
  1. Safety and tolerability of PIF-1 in steroid-resistant patients who develop acute GVHD, as evidenced by clinical and laboratory indices [ Time Frame: within 90 days after first PIF-1 injection ]

Secondary Outcome Measures :
  1. Therapeutic effect of PIF-1 on participants' acute GVHD status, as determined by comparison with the clinical and laboratory indices before intervention [ Time Frame: within 90 days after first PIF-1 injection ]

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria:

  • Morbidity unrelated to GVHD

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00517907

Contact: Reuven Or, MD +972-2-677-8357

Hadassah Medical Organization Not yet recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD    +972-2-677-6095   
Contact: Hadas Lemberg, PhD    +972-2-677-7572   
Principal Investigator: Reuven Or, MD         
Sponsors and Collaborators
Hadassah Medical Organization
BioIncept LLC
Principal Investigator: Reuven Or, MD Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel

Responsible Party: Reuven Or, MD, Bone Marrow Transpl., Cancer Immunother. & Immunobio. Res. Ctr., Hadassah Univ. Hosp. Identifier: NCT00517907     History of Changes
Other Study ID Numbers: PIF1BMT-HMO-CTIL
First Posted: August 17, 2007    Key Record Dates
Last Update Posted: June 11, 2015
Last Verified: August 2008

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases