Acute Myeloid LeukemiaPhase 1/2NCT02328755

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

A Phase 1/2 study testing peg-IFN-α, Hematopoietic Cell Transplant (HCT) and Tacrolimus in people with Acute Myeloid Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: peg-IFN-α, Hematopoietic Cell Transplant (HCT) and Tacrolimus
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: Jan 2015to 25 Mar 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 11Show fewer

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

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

Read the 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.

Conditions: Acute Myeloid Leukemia
Being tested: peg-IFN-α, Hematopoietic Cell Transplant (HCT), Tacrolimus, Methotrexate
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

peg-IFN-αDrug
Also called PEGASYS®
Hematopoietic Cell Transplant (HCT)Procedure or surgery
TacrolimusDrug
Calcineurin inhibitor administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis. Cyclosporine may be substituted if patients cannot tolerate tacrolimus.
MethotrexateDrug
Administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.

Study groups in NCT02328755
Study group	Role	What they receive
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 Receives: Drug: peg-IFN-α; Procedure: Hematopoietic Cell Transplant (HCT); Drug: Tacrolimus; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 6 Months Post HCT

Secondary outcomes (4)

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
Measured: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Phase 2: Event Free Survival Time
Defined for this study as Leukemia Free Survival, and estimated using Kaplan-Meier methods.
Measured: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
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.
Measured: 6 months
Non-Relapse Mortality
The cumulative incidence of non-relapse mortality is estimated by proportional hazard models methods.
Measured: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 201525 Mar 2019

First posted31 Dec 2014 (estimated)
Study startJan 2015
Primary completion25 Mar 2019
Study completion25 Mar 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02328755
Sponsor's protocol ID: UMCC 2014.107
Other IDs: HUM00093471
Status last verified: Oct 2021
First submitted: 11 Nov 2014
Last updated: 6 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 34607341

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
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Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
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Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
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ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
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All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Targeting Cross-presentation With Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in High Risk Acute Myeloid Leukemia
ClinicalTrials.gov ID: NCT02328755
Acronym / sponsor ID: UMCC 2014.107
Conditions: Acute Myeloid Leukemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Study start: Jan 2015
Primary completion: 25 Mar 2019 (actual)
Study completion: 25 Mar 2019 (actual)
First posted: 31 Dec 2014 (estimated)
Results: Posted 6 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
peg-IFN-α	Experimental	Drug: peg-IFN-α, Procedure: Hematopoietic Cell Transplant (HCT), Drug: Tacrolimus, Drug: Methotrexatepeg-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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
peg-IFN-αAlso: PEGASYS®	Drug	peg-IFN-α
Hematopoietic Cell Transplant (HCT)	Procedure or surgery	peg-IFN-α
TacrolimusCalcineurin inhibitor administered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis. Cyclosporine may be substituted if patients cannot tolerate tacrolimus.	Drug	peg-IFN-α
MethotrexateAdministered along with HCT for Graft Versus Host Disease (GVHD) prophylaxis.	Drug	peg-IFN-α

Primary outcome

Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α
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.
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
Time frame: 6 Months Post HCT
The cumulative incidence of relapse, estimated using proportional hazard model for the competing risk of non-relapse mortality (NRM).

4 secondary outcomes

Phase 2: Overall Survival Time
Time frame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Phase 2: Event Free Survival Time
Time frame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.
Acute GVHD
Time frame: 6 months
Non-Relapse Mortality
Time frame: 1 year or until study stops, whichever is later. Median time of follow-up was 25 months.

Results and safety

Results posted to the registry on 6 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Level 1, 90 mcg Peg-IFN-α	3	0
Dose Level 2, 180 mcg Peg-IFN-α	33	31

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

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.. Number. Unit: mcg

Measure	Peg-IFN-α n = 36
Value	180

Population analysed: All participants (n=36)

Primary outcome: Phase 2: Number of Patients That Relapse

Time frame: 6 Months Post HCT. Number. Unit: percentage of participants

Measure	Dose Level 1 - 90 mg Peg-IFN-α n = 3	Dose Level 2 - 180 mg Peg-IFN-α n = 33
Phase II MTD (180mcg) participants with fully matched donor HCT	–	39
All participants	67	39

Dose Level 2 - 180 mg Peg-IFN-α: cumulative incidence: 0.39 (95% CI 0.24 to 0.58)

Population analysed: 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)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I/Dose Level 1 - 90 mcg	2 of 3 (66.7%)	0 of 3 (0%)	2 of 3
Phase 2/Dose Level 2 - 180 mcg Peg-IFN-α	8 of 33 (24.2%)	0 of 33 (0%)	22 of 33

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34607341Magenau 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John M Magenau, M.D. principal investigator

University of Michigan Rogel Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02328755, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2021.