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

Condition(s) targeted: Graft Versus Host Disease

Intervention: stem cell transplant (Procedure); tacrolimus (standard GVHD prophylaxis) (Drug); mycophenolate (standard GVHD prophylaxis) (Drug); etanercept (Drug); methoxsalen (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Michigan Cancer Center

Official(s) and/or principal investigator(s):
John E Levine, MD, Principal Investigator, Affiliation: University of Michigan Cancer Center

Overall contact:
Cancer Answer Line, Phone: 1 (800) 865 -1125, Email: canceranswerline@umich.edu

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.

Official title: Addition of Etanercept and Extracorporeal Photopheresis to Standard GVHD Prophylaxis in Patients Undergoing Reduced Intensity Unrelated Donor Hematopoietic Stem Cell Transplant

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: Patients who are alive, in remission, and at very low dose steroids at 6 months post-transplant

Secondary outcome:

Incidence of acute GVHD grades 2-4 and chronic GVHD in this study population

Effect of this prophylaxis regimen on plasma markers of inflammation after transplant

To correlate regulatory T cell numbers post-transplant with GVHD outcomes

To correlate donor and host inflammatory cytokine gene polymorphisms on clinical outcomes observed during the trial

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

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

Cancer Answer Line, Phone: 1 (800) 865 -1125, Email: canceranswerline@umich.edu

University of Michigan Cancer Center, Ann Arbor, Michigan 48109, United States; Recruiting
John E Levine, MD, Phone: 734-936-8456
John E Levine, MD, MS, Principal Investigator

Starting date: March 2009
Last updated: November 14, 2011