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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by Hadassah Medical Organization.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
BioIncept LLC
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00517907
First received: August 16, 2007
Last updated: August 14, 2008
Last verified: August 2008
  Purpose

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 Intervention Phase
Graft vs Host Disease
Drug: Preimplantation factor (PIF-1)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 6
Study Start Date: January 2009
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   14 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute steroid-resistant GVHD post matched BMT

Exclusion Criteria:

  • Morbidity unrelated to GVHD
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517907

Contacts
Contact: Reuven Or, MD +972-2-677-8357 reuvenor@hadassah.org.il

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

No publications provided

Responsible Party: Reuven Or, MD, Bone Marrow Transpl., Cancer Immunother. & Immunobio. Res. Ctr., Hadassah Univ. Hosp.
ClinicalTrials.gov Identifier: NCT00517907     History of Changes
Other Study ID Numbers: PIF1BMT-HMO-CTIL
Study First Received: August 16, 2007
Last Updated: August 14, 2008
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

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

ClinicalTrials.gov processed this record on October 19, 2014