Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in Acute Myeloid Leukemia

This protocol is an open label, single arm, non-randomized, phase I / II clinical trial
investigating the use of pegylated interferon alpha-2a (peg-IFN-α, Pegasys®, Genentech) for
prevention of relapse in acute myeloid leukemia (AML) not in remission at the time of
allogeneic hematopoietic stem cell transplantation (HCT). The inability to attain remission
status following induction therapy for AML remains a significant problem and is associated
with poor outcomes. While HCT remains a curative option, its activity in the setting of
relapsed or refractory AML is significantly diminished due to high relapse.

The anti-leukemic properties of HCT are primarily attributed to the combined effects of 1)
pre - transplant chemotherapy (termed conditioning) and 2) the immunologic effects of donor
cells (termed graft-versus-leukemia or GVL). While increasing the intensity of conditioning
reduces relapse, this strategy has historically been associated with greater toxicity.
Alternatively, improving GVL without added toxicity (particularly graft-versus-host disease)
represents an alternative strategy for limiting relapse and improving outcomes, which is the
aim of this protocol.

IFN-α, FDA approved for viral hepatitis, has demonstrated anti-tumor activity in several
hematologic malignancies including myeloproliferative diseases and AML. IFN-α has also shown
feasibility in the treatment of post HCT relapse by eliciting durable clinical responses,
without significant toxicity. Recent insights from pre-clinical studies in HCT have now
identified a central role of IFN-α in enhancing antigen presentation, thereby promoting
leukemia specific T cell responses (GVL) without GVHD. In this protocol, the investigators
propose to administer peg-IFN-α to prevent relapse by increasing GVL responses in patients
with relapsed and refractory AML not in remission at the time of HCT.

Inclusion Criteria:

- Patient must have AML not in remission or at very high risk for HCT (Hematopoietic
Cell Transplantation) relapse.

- For newly diagnosed AML, patients must have achieved two consecutive induction
attempts without achieving complete remission

- For patients initially in complete remission whose AML relapses > 6 months after
preceding remission, one re-induction must be attempted to be eligible

- For AML patients with early relapse, in whom the preceding remission is shorter than 6
months duration, no re-induction regimen is necessary to be eligible

- Patients with antecedent MDS (Myelodysplastic Syndrome) who progress to AML may have
therapies rendered during both phases counted towards these requirements.

- Patients with poor cytogenetic or molecular risk associated with very high risk for
relapse after HCT may proceed without provisions for prior treatment. However, they
must have received at least one induction attempt.

- Availability of an 8/8 matched donor at A, B, C, and DR loci. Mismatch at HLA DQ are
permissible. Matched related or unrelated donors are acceptable Peripheral blood or
bone marrow stem cells are acceptable

- Patients must be ≥ 18 years of age and considered a candidate for HCT

- Karnofsky ≥ 70% (Karnofsky performance status is measure of a cancer patients general
well being and activities of daily life. Scores range from 100 to 0 where 100 is
perfect health and 0 is death

- Patients must meet acceptable organ function criteria: Total Bilirubin ≤2.5 mg%; AST
(Aspartate transaminase) and ALT (Alanine transaminase) <5.0 X institutional upper
limit of normal; GFR (Glomerular filtration rate) >40 mL/min/1.73 m2 for patients with
creatinine levels above institutional normal; Lung function tests (DLCO, FEV1, FVC) >
50%; Ejection fraction > 50%

- All patients must sign an informed consent

- Women and men of child-bearing potential must agree to use adequate contraception

Exclusion Criteria:

- Prior chemotherapy treatment for AML within 21 days from the initiation of HCT
conditioning

- Patients may NOT have evidence or symptoms of CNS disease at the time of enrollment

- HIV or HTLV1 / HTLV2 (Human T-lymphotrophic virus) (seropositivity and/or PCR
positivity)

- Patients less than 18 years of age

- Pregnant and nursing mothers are excluded from this study

- Patients with untreated or uncontrolled neuropsychiatric illness

- Any physical or psychological condition that, in the opinion of the investigator,
would pose unacceptable risk to the patient

- Uncontrolled infections