Addition of Etanercept and Extracorporeal Photopheresis (ECP) to Standard Graft-Versus-Host Disease (GVHD) Prophylaxis in Stem Cell Transplant
Condition: Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: stem cell transplant; tacrolimus (standard GVHD prophylaxis); mycophenolate (standard GVHD prophylaxis); etanercept; methoxsalen
Intervention description: reduced intensity, matched unrelated donor stem cell transplant; 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; 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.; 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); 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.
Intervention MeSH terms: Etanercept; Methoxsalen; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Healthy volunteers: No
Keywords: GVHD

Summary:

      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.
    

Eligibility 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