Ann Arbor, Michigan 48109


Purpose:

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).


Study summary:

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.


Criteria:

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


NCT ID:

NCT02328755


Primary Contact:

Principal Investigator
John M Magenau, M.D.
University of Michigan Cancer Center

John M Magenau, M.D.
Phone: 734/936-8785
Email: johnmage@umich.edu


Backup Contact:

N/A


Location Contact:

Ann Arbor, Michigan 48109
United States

John M Magenau, M.D.
Phone: 734-936-8785
Email: johnmage@umich.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: June 25, 2018

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

If you would like to be contacted by the clinical trial representative please fill out the form below.