Addition of Etanercept and Extracorporeal Photopheresis (ECP) to Standard Graft-Versus-Host Disease (GVHD) Prophylaxis in Stem Cell Transplant - Full Text View

Sponsors and Collaborators:	University of Michigan Cancer Center Therakos Amgen
Information provided by:	University of Michigan Cancer Center
ClinicalTrials.gov Identifier:	NCT00639717

Purpose

This research study investigates the benefits and possible risks of adding both etanercept (Enbrel) and ECP (extracorporeal photopheresis) to the conventional preventative (or prophylactic) treatments for graft-versus-host disease (GVHD). GVHD is a common, serious, and too often fatal, complication after matched unrelated donor stem cell transplantation, regardless of the pre-transplant conditioning regimen used (full or reduced intensity).

Reduced intensity transplants which employ lower doses of chemotherapy during the conditioning phase of the transplant, are less toxic than full intensity transplants. Reduced intensity transplants may extend the unrelated donor transplant option to older patients or to patients with existing medical conditions or illness, where a full intensity transplant is not possible. To be successful, reduced intensity transplants need to offset any lower effectiveness in killing cancer cells during the conditioning phase, with the establishment of a donor cell, graft-versus-leukemia effect (GVL). The GVL effect and GVHD are associated with each other and therefore, the goal of GVHD prophylaxis for this study is not so much to prevent all GVHD, but rather to prevent serious and fatal acute GVHD.

Most GVHD-related deaths are either the direct consequence of severe GVHD or from infections associated with intense immunosuppression, a consequence of the standard treatments for acute GVHD, which almost always include high-dose steroids. A more effective prophylaxis therapy that allows for the GVL effect to develop, while limiting the exposure to high-dose steroids may reduce transplant mortality and morbidity. We also will study how key chemical and cellular factors relate to clinical outcome.

Condition	Intervention	Phase
Graft Versus Host Disease	Procedure: stem cell transplant Drug: tacrolimus (standard GVHD prophylaxis) Drug: mycophenolate (standard GVHD prophylaxis) Drug: etanercept Drug: methoxsalen	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Tacrolimus Methoxsalen Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Etanercept Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Addition of Etanercept and Extracorporeal Photopheresis to Standard GVHD Prophylaxis in Patients Undergoing Reduced Intensity Unrelated Donor Hematopoietic Stem Cell Transplant

Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:

Patients who are alive, in remission, and at very low dose steroids at 6 months post-transplant [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of acute GVHD grades 2-4 and chronic GVHD in this study population [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
Effect of this prophylaxis regimen on plasma markers of inflammation after transplant [ Time Frame: 100 days ] [ Designated as safety issue: No ]
To correlate regulatory T cell numbers post-transplant with GVHD outcomes [ Time Frame: 180 days ] [ Designated as safety issue: No ]
To correlate donor and host inflammatory cytokine gene polymorphisms on clinical outcomes observed during the trial [ Time Frame: 180 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	October 2008
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental etanercept and ECP in addition to standard GVHD prevention	Procedure: stem cell transplant reduced intensity, matched unrelated donor stem cell transplant Drug: tacrolimus (standard GVHD prophylaxis) Tacrolimus(or cyclosporine when necessary) Tacrolimus will begin on day -3, IV or oral. Target trough level for tacrolimus is 8-12 ng/ml. In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant Drug: mycophenolate (standard GVHD prophylaxis) Mycophenolate will begin on day 0 at 10 mg/kg/dose (up to 1 gram per dose) every 8 hours orally or intravenously and will continue until day 28. Drug: etanercept Etanercept will be given at a dose 0.4 mg/kg (actual weight) up to a maximum dose of 25 mg, subcutaneously, twice weekly from day 0 to day 56 (16 doses) Drug: methoxsalen Methoxsalen (UVADEX) treatments by Extracorporeal photopheresis (ECP) will be started day +28 post transplant and given weekly. On day +70 post transplant ECP frequency will be given every other week. On day +100 post transplant ECP will be given monthly until day +180 and stopped.

Arms

Assigned Interventions

1: Experimental

etanercept and ECP in addition to standard GVHD prevention

Procedure: stem cell transplant

reduced intensity, matched unrelated donor stem cell transplant

Drug: tacrolimus (standard GVHD prophylaxis)

Tacrolimus(or cyclosporine when necessary)

Tacrolimus will begin on day -3, IV or oral.

Target trough level for tacrolimus is 8-12 ng/ml.

In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant

Drug: mycophenolate (standard GVHD prophylaxis)

Mycophenolate will begin on day 0 at 10 mg/kg/dose (up to 1 gram per dose) every 8 hours orally or intravenously and will continue until day 28.

Drug: etanercept

Etanercept will be given at a dose 0.4 mg/kg (actual weight) up to a maximum dose of 25 mg, subcutaneously, twice weekly from day 0 to day 56 (16 doses)

Drug: methoxsalen

Methoxsalen (UVADEX) treatments by Extracorporeal photopheresis (ECP) will be started day +28 post transplant and given weekly.

On day +70 post transplant ECP frequency will be given every other week.

On day +100 post transplant ECP will be given monthly until day +180 and stopped.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Candidate for unrelated donor (allogeneic) HSCT for hematologic conditions, either malignant or non-malignant.
Donor can be unrelated marrow, blood or cord blood.
Any disease for which unrelated donor transplant is appropriate is eligible except:
- Progressive or poorly controlled malignancies for which the likelihood of durable disease control [i.e., patients expected to have at least 6 months PFS from date of transplant] is <25%.
- This determination of likelihood of durable disease control must take into account the patient's disease status and consideration of the agents and doses used in the reduced intensity conditioning regimen.
- The determination of adequate disease control will be certified by the PI or designee on the eligibility checklist.
- Patients may be consented to this trial based on disease control at the time of consent, but later removed from the trial prior to initiation of transplant conditioning regimen if disease status confirmation between consenting and transplant changes. In the event this occurs these patients will be replaced.
Must be receiving a recognized reduced intensity transplant as determined by the University of Michigan Blood and Marrow Transplantation Program.
Patients age 50 or older are eligible based on age.
Patients may be <50 years old if they are eligible for a reduced intensity conditioning regimen based on disease type (eg, indolent lymphoma) or if comorbidities preclude a full-intensity transplant.
Patients must have adequate venous access by either peripheral vein or central line so that ECP can be performed.
Patients must be expected to tolerate the fluid shifts associated with ECP. The primary reason for expected intolerance of ECP is small size (ie, <30kg weight), but other factors may also be considered in this determination.

Exclusion Criteria:

Not a candidate for a reduced intensity transplant conditioning regimen (based on the current U-M BMT program clinical guidelines).
Patient has a suitable related donor available for transplant.
Karnofsky or Lansky performance status of < 50% at the time of admission for HSCT
Patients with evidence of HIV infection or other opportunistic infection including but not limited to Tuberculosis and Histoplasmosis.
Patients with active bacterial, fungal or viral infection not responding to treatment.
Any medical or psychological conditions that would keep the patient from complying with the protocol and/or would markedly increase the morbidity and mortality from the procedure.
Pregnancy.
T-cell depleted allograft

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639717

Contacts

Contact: Cancer Answer Line

1 (800) 865 -1125

canceranswerline@umich.edu

Locations

United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan Cancer Center

Therakos

Amgen

Investigators

Principal Investigator:

John E Levine, MD

University of Michigan Cancer Center

More Information

Responsible Party:	University of Michigan Cancer Center ( John E. Levine MD /Associate Professor, Departments of Pediatrics and Int. Medicine )
Study ID Numbers:	umcc 2008.003
Study First Received:	March 11, 2008
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00639717
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:

GVHD

Study placed in the following topic categories:

Cyclosporine
Methoxsalen
Graft versus host disease
Mycophenolate mofetil
Graft vs Host Disease

Tacrolimus
TNFR-Fc fusion protein
Cyclosporins
Homologous wasting disease

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immune System Diseases
Immunologic Factors
Physiological Effects of Drugs
Gastrointestinal Agents
Immunosuppressive Agents
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents

Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on January 16, 2009