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

Primary Purpose

Acute Myeloid Leukemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

peg-IFN-α

Hematopoietic Cell Transplant (HCT)

Tacrolimus

Methotrexate

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

peg-IFN-α

Arm Description

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

Outcomes

Primary Outcome Measures

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.

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).

Secondary Outcome Measures

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

Phase 2: Event Free Survival Time

Defined for this study as Leukemia Free Survival, and estimated using Kaplan-Meier methods.

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.

Non-Relapse Mortality

The cumulative incidence of non-relapse mortality is estimated by proportional hazard models methods.

Full Information

NCT ID

NCT02328755

First Posted

November 11, 2014

Last Updated

October 1, 2021

Sponsor

University of Michigan Rogel Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT02328755

Brief Title

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

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

January 2015 (undefined)

Primary Completion Date

March 25, 2019 (Actual)

Study Completion Date

March 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

peg-IFN-α

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

peg-IFN-α

Other Intervention Name(s)

PEGASYS®

Intervention Type

Procedure

Intervention Name(s)

Hematopoietic Cell Transplant (HCT)

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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.

Title

Phase 2: Number of Patients That Relapse

Description

The cumulative incidence of relapse, estimated using proportional hazard model for the competing risk of non-relapse mortality (NRM).

Time Frame

6 Months Post HCT

Secondary Outcome Measure Information:

Title

Phase 2: Overall Survival Time

Description

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

Time Frame

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

Title

Phase 2: Event Free Survival Time

Description

Defined for this study as Leukemia Free Survival, and estimated using Kaplan-Meier methods.

Time Frame

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

Title

Acute GVHD

Description

Grade 2-4 Acute GVHD estimated using proportional hazards ratio. Graded according to CTCAE v. 4.0; higher grades represent more severe events.

Time Frame

6 months

Title

Non-Relapse Mortality

Description

The cumulative incidence of non-relapse mortality is estimated by proportional hazard models methods.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John M Magenau, M.D.

Organizational Affiliation

University of Michigan Rogel Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34607341

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.

Results Reference

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

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