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

Acute Myeloid Leukemia Clinical Trial

Official title:

Targeting Cross-presentation With Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in High Risk Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02328755
• Other study ID #: UMCC 2014.107
• Secondary ID: HUM00093471
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2015
• Est. completion date: March 25, 2019

Study information

• Verified date: October 2021
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 25, 2019
• Est. primary completion date: March 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• peg-IFN-a

Procedure:
• Hematopoietic Cell Transplant (HCT)

Drug:
• Tacrolimus
Calcineurin inhibitor administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis. Cyclosporine may be substituted if patients cannot tolerate tacrolimus.
• Methotrexate
Administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-a	The dose level assigned to the most participants is selected as the MTD. Participants from the arms for dose level 1 (90mcg, 3 participants) and dose level 2 (180mcg, 33 participants) were analyzed together to determine the MTD. Dosage levels are determined by dose-limiting toxicities (DLTs). Only DLTs encountered during the treatment period, prior to day 56 post HCT (or 14 days after final treatment, whichever comes later), are counted. DLTs after the treatment period are counted only if they reflect an ongoing toxicity that initiated in the treatment period.	Up to day 56 post-transplant or up to 14 days after final treatment with peg-IFN-a, whichever comes later. Data was collected up to 63 days.
Primary	Phase 2: Number of Patients That Relapse	The cumulative incidence of relapse, estimated using proportional hazard model for the competing risk of non-relapse mortality (NRM).	6 Months Post HCT
Secondary	Phase 2: Overall Survival Time	Estimated using Kaplan-Meier methods, overall survival (OS) will be calculated from the day of transplantation (day 0) until death; shown at 6 month and 2 year estimates	1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Secondary	Phase 2: Event Free Survival Time	Defined for this study as Leukemia Free Survival, and estimated using Kaplan-Meier methods.	1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Secondary	Acute GVHD	Grade 2-4 Acute GVHD estimated using proportional hazards ratio. Graded according to CTCAE v. 4.0; higher grades represent more severe events.	6 months
Secondary	Non-Relapse Mortality	The cumulative incidence of non-relapse mortality is estimated by proportional hazard models methods.	1 year or until study stops, whichever is later. Median time of follow-up was 25 months.