Clinical trial NCT02328755: Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in Acute Myeloid Leukemia
Official title: Targeting Cross-presentation With Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in High Risk Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2014-12-31
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Eligibility 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.
* 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

Primary outcomes:
measure: Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α
timeFrame: Up to day 56 post-transplant or up to 14 days after final treatment with peg-IFN-α, whichever comes later. Data was collected up to 63 days.
measure: Phase 2: Number of Patients That Relapse
timeFrame: 6 Months Post HCT
Secondary outcomes:
measure: Phase 2: Overall Survival Time
timeFrame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
measure: Phase 2: Event Free Survival Time
timeFrame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
measure: Acute GVHD
timeFrame: 6 months
measure: Non-Relapse Mortality
timeFrame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: John M Magenau, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magenau JM, Peltier D, Riwes M, Pawarode A, Parkin B, Braun T, Anand S, Ghosh M, Maciejewski J, Yanik G, Choi SW, Talpaz M, Reddy P. Type 1 interferon to prevent leukemia relapse after allogeneic transplantation. Blood Adv. 2021 Dec 14;5(23):5047-5056. doi: 10.1182/bloodadvances.2021004908.