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

NCT02328755 | Completed Phase 1 Results DMC

• 2 other identifiers: UMCC 2014.107HUM00093471
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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).

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α

  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-α, whichever comes later. Data was collected up to 63 days.

• 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 Outcomes (4)

• Phase 2: Overall Survival Time

  1 year or until study stops, whichever is later. Median time of follow-up was 25 months.

• Phase 2: Event Free Survival Time

  1 year or until study stops, whichever is later. Median time of follow-up was 25 months.

• Acute GVHD

  6 months

• Non-Relapse Mortality

  1 year or until study stops, whichever is later. Median time of follow-up was 25 months.

Study Arms (1)

peg-IFN-α

EXPERIMENTAL

peg-IFN-α will be administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It will be administered by subcutaneous injection every 14 days beginning with dose level 1. Dose Level -1 - 45mcg Dose Level 1 - 90mcg Dose Level 2 - 180 mcg

Drug: peg-IFN-α; Procedure: Hematopoietic Cell Transplant (HCT); Drug: Tacrolimus; Drug: Methotrexate

Interventions

peg-IFN-α DRUG

Also known as: PEGASYS®

peg-IFN-α

Hematopoietic Cell Transplant (HCT) PROCEDURE

peg-IFN-α

Tacrolimus DRUG

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

peg-IFN-α

Methotrexate DRUG

Administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.

peg-IFN-α

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 34607341 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

peginterferon alfa-2a; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: John Magenau
• Organization: University of Michigan

johnmage@med.umich.edu

734 936-8785

Study Officials

• John M Magenau, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: December 31, 2014
• Study Start: January 1, 2015
• Primary Completion: March 25, 2019
• Study Completion: March 25, 2019
• Last Updated: October 6, 2021
• Results First Posted: October 6, 2021

Record last verified: 2021-10

Locations

US (1)