Trial Outcomes & Findings for Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in Acute Myeloid Leukemia (NCT NCT02328755)

Last Updated: 2021-10-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

37 participants

Primary outcome 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.

Results posted on

2021-10-06

Participant Flow

One person did not start study treatment; no participants were assigned or de-escalated to Dose Level -1 (45mcg).

Participant milestones

Participant milestones
Measure	Dose Level 1, 90 mcg Peg-IFN-α 90 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.	Dose Level 2, 180 mcg Peg-IFN-α 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Overall Study STARTED	3	33
Overall Study COMPLETED	0	31
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - 90 mcg Peg-IFN-α n=3 Participants Dose Level 1 - 90 mcg peg-IFN-α administered prior to hematopoietic cell transplant (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days beginning with dose level 1.	Dose Level 2 - 180 mcg Peg-IFN-α n=33 Participants Dose Level 2 - 180 mcg peg-IFN-α administered prior to hematopoietic cell transplant (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days beginning with dose level 1.	Total n=36 Participants Total of all reporting groups
Age, Continuous	56 years n=99 Participants	60 years n=107 Participants	60 years n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	13 Participants n=107 Participants	14 Participants n=206 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	20 Participants n=107 Participants	22 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=99 Participants	33 Participants n=107 Participants	36 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	32 Participants n=107 Participants	35 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	3 participants n=99 Participants	33 participants n=107 Participants	36 participants n=206 Participants
Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI)CT-Cl	5 units on a scale n=99 Participants	3 units on a scale n=107 Participants	3 units on a scale n=206 Participants
Disease Status at HCT Not in remission	3 Participants n=99 Participants	32 Participants n=107 Participants	35 Participants n=206 Participants
Disease Status at HCT Remission	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Cytogenic risk Poor	2 Participants n=99 Participants	16 Participants n=107 Participants	18 Participants n=206 Participants
Cytogenic risk Intermediate	1 Participants n=99 Participants	16 Participants n=107 Participants	17 Participants n=206 Participants
Cytogenic risk Unknown	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Disease Risk Score Greater or equal to 3	2 Participants n=99 Participants	19 Participants n=107 Participants	21 Participants n=206 Participants
Disease Risk Score 2	1 Participants n=99 Participants	11 Participants n=107 Participants	12 Participants n=206 Participants
Disease Risk Score 1	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Time to HCT from AML Diagnosis	98 days n=99 Participants	192 days n=107 Participants	142 days n=206 Participants
Donor Type Unrelated	2 Participants n=99 Participants	18 Participants n=107 Participants	20 Participants n=206 Participants
Donor Type Related	1 Participants n=99 Participants	15 Participants n=107 Participants	16 Participants n=206 Participants
Human Leukocyte Antigen match Yes	3 Participants n=99 Participants	31 Participants n=107 Participants	34 Participants n=206 Participants
Human Leukocyte Antigen match No	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Donor Source Peripheral Blood Stem Cells	2 Participants n=99 Participants	29 Participants n=107 Participants	31 Participants n=206 Participants
Donor Source Bone Marrow	1 Participants n=99 Participants	4 Participants n=107 Participants	5 Participants n=206 Participants

PRIMARY outcome

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.

Population: All participants (n=36)

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=36 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α	180 mcg	—

PRIMARY outcome

Timeframe: 6 Months Post HCT

Population: The first row shows analysis for recipients of HLA-matched HCT who received the phase II MTD (180mcg) peg-IFN-α (n=31); the second row shows all participants (n=36)

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

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=3 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α n=33 Participants 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Phase 2: Number of Patients That Relapse Phase II MTD (180mcg) participants with fully matched donor HCT	—	39 percentage of participants
Phase 2: Number of Patients That Relapse All participants	67 percentage of participants	39 percentage of participants

SECONDARY outcome

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

Population: Some rows show analysis for recipients of HLA-matched HCT who received the phase II MTD (180mcg) peg-IFN-α(n=31); for 6 month data, the additional row shows all participants (n=36)

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

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=3 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α n=33 Participants 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Phase 2: Overall Survival Time 6 months (Phase II MTD [180 mcg] participants with fully matched donor HCT)	—	55 percentage of participants
Phase 2: Overall Survival Time 6 months - all participants	33 percentage of participants	55 percentage of participants
Phase 2: Overall Survival Time 2 years (Phase II MTD [180 mcg] participants with fully matched donor HCT)	—	33 percentage of participants

SECONDARY outcome

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

Population: Recipients of HLA-matched HCT who received phase II MTD (180mcg) peg-IFN-α (n=31)

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

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=31 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Phase 2: Event Free Survival Time 6 months	48 percentage of participants Interval 34.0 to 70.0	—
Phase 2: Event Free Survival Time 2 years	28 percentage of participants Interval 15.0 to 52.0	—

SECONDARY outcome

Timeframe: 6 months

Population: Recipients of HLA-matched HCT who received phase II MTD (180mcg) peg-IFN-a (n=31)

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

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=31 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Acute GVHD	39 percentage of participants Interval 24.0 to 58.0	—

SECONDARY outcome

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

Population: Recipients of HLA-matched HCT who received phase II MTD (180mcg) peg-IFN-α (n=31)

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

Outcome measures

Outcome measures
Measure	Peg-IFN-α n=31 Participants peg-IFN-α was administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It was 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 peg-IFN-α It was begun at 90 mcg, would have been reduced back to 45 mcg if necessary, and after 3 participants it was increased to 180 mcg.	Dose Level 2 - 180 mg Peg-IFN-α 180 mcg peg-IFN-α administered prior to hematopoietic cell transplantation (HCT) and at three subsequent time points post HCT (maximum of 4 doses) every 14 days.
Non-Relapse Mortality 6 months	13 percentage of participants Interval 5.0 to 31.0	—
Non-Relapse Mortality 2 years	25 percentage of participants Interval 12.0 to 46.0	—

Adverse Events

Phase I/Dose Level 1 - 90 mcg

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

Phase 2/Dose Level 2 - 180 mcg Peg-IFN-α

Serious events: 8 serious events

Other events: 0 other events

Deaths: 22 deaths

Serious adverse events

Serious adverse events
Measure	Phase I/Dose Level 1 - 90 mcg n=3 participants at risk peg-IFN-α 90 mcg administered prior to hematopoietic cell transplant (HCT) and at three subsequent time points post HCT (maximum of 4 doses), every 14 days. Tacrolimus: Calcineurin inhibitor administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis. Cyclosporine could be substituted if patients cannot tolerate tacrolimus. Methotrexate: Administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.	Phase 2/Dose Level 2 - 180 mcg Peg-IFN-α n=33 participants at risk peg-IFN-α 180 mcg administered prior to hematopoietic cell transplant (HCT) and at three subsequent time points post HCT (maximum of 4 doses), every 14 days. Tacrolimus: Calcineurin inhibitor administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis. Cyclosporine could be substituted if patients cannot tolerate tacrolimus. Methotrexate: Administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.
Skin and subcutaneous tissue disorders Rash	66.7% 2/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	6.1% 2/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Respiratory, thoracic and mediastinal disorders Pulmonary	0.00% 0/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	6.1% 2/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Musculoskeletal and connective tissue disorders Arthritis	33.3% 1/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	0.00% 0/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Cardiac disorders Hypertension	33.3% 1/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	0.00% 0/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Cardiac disorders Hypotension	0.00% 0/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	3.0% 1/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	3.0% 1/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Hepatobiliary disorders Liver Function Test elevation	0.00% 0/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	3.0% 1/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.
Immune system disorders Graft Failure	0.00% 0/3 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.	3.0% 1/33 • The assessment and reporting period for all adverse events will occur from the first day the treatment with peg-IFN-α is administered until day +56 post transplant or until 14 days after the last dose of peg-IFN-α is administered, whichever comes last. Adverse event data were collected up to 63 days. All-Cause Mortality assessed up to 4 years; median of 25 months. Only grade \>=3 events were recorded; infectious disease and hematologic events were not included.

Other adverse events

Adverse event data not reported

Additional Information

John Magenau

University of Michigan

Phone: 734 936-8785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place