Pegylated Interferon Alfa-2a for Myelofibrosis

(ATIOM Trial)

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Utah

Must not be taking: Investigational agents

Disqualifiers: Graft-versus-host, Cardiovascular disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test pegylated interferon alfa-2a, an interferon medication, for treating myelofibrosis—a condition where scar tissue forms in the bone marrow and affects blood cell production. The goal is to determine the safest and most effective dose of the treatment after a bone marrow transplant. Individuals diagnosed with primary or secondary myelofibrosis who have undergone a specific type of bone marrow transplant may qualify. Initially, the trial will test different doses to ensure safety before selecting the best one for further study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, it mentions that a washout period (time without taking certain medications) of at least five half-lives is required for prohibited medications before starting the treatment. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that pegylated interferon alfa-2a is likely to be safe for humans?

Research shows that pegylated interferon alfa-2a is usually well-tolerated by patients. In past studies, some people experienced side effects like mild liver inflammation, occurring in about 21.6% of cases. Only a small number, around 1.8%, faced more serious liver issues. Other side effects included an underactive thyroid in 3.7% of participants and skin rash in a few others.

These results suggest that while some risks exist, the treatment is relatively safe for most people. This trial is in its early stage, focusing on ensuring the treatment's safety and determining the right dose. The treatment already has approval for other conditions, which provides some confidence in its safety. However, it's important to remember that individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pegylated Interferon Alfa-2a is unique because it offers a potentially new approach for treating myelofibrosis by utilizing a pegylated form of interferon. This modification allows the drug to stay in the body longer, potentially reducing the frequency of dosing compared to traditional interferon treatments. Researchers are excited about this treatment because it may offer improved safety and tolerability, which are significant considerations for patients with this condition. Unlike some existing treatments that mainly focus on symptom management, Pegylated Interferon Alfa-2a could directly target the underlying disease process, providing a more comprehensive therapeutic benefit.

What evidence suggests that pegylated interferon alfa-2a might be an effective treatment for myelofibrosis?

Research has shown that pegylated interferon alfa-2a is a promising treatment for certain blood cancers called myeloproliferative neoplasms. Studies have found it to be a safe and effective way to reduce abnormal blood cells. Notably, it provides long-lasting benefits, continuing to work well over time. One study found that pegylated interferon led to better results compared to standard treatments. These findings suggest that pegylated interferon alfa-2a could also help patients with myelofibrosis, a related condition. Participants in this trial will receive pegylated interferon alfa-2a to evaluate its safety and effectiveness for myelofibrosis. ^{1 2 3 4 5}

Who Is on the Research Team?

Sagar A. Patel, MD

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with primary or secondary myelofibrosis who are eligible for a bone marrow transplant. They must be physically able to undergo the procedure, have a perfect match donor, and women must be post-menopausal or surgically sterile.

Inclusion Criteria

I can have a bone marrow biopsy as part of my pre-transplant evaluation.

I can take care of myself but might not be able to do heavy physical work.

I am not pregnant or I have been through menopause.

Exclusion Criteria

I have not had radiotherapy in the last 6 weeks.

I haven't had cancer treatment or experimental therapy recently.

I have a history of mental health issues, autoimmune disease, or pancreatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Pegylated interferon alfa-2a administered after alloHCT to assess dose-limiting toxicities and determine the recommended phase 2 dose

12 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes such as leukemia-free survival and incidence of GVHD

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pegylated Interferon Alfa-2a

Trial Overview The study tests Pegylated interferon alpha2a in patients after bone marrow transplantation. It's an open-label Phase 1 trial focusing on finding the safest dose that doesn't cause too many side effects (dose-limiting toxicities).

How Is the Trial Designed?

Group I: Treatment: All Patients Experimental Treatment 1 Intervention

A 3+3 dose de-escalation design will be used to determine the recommended phase 2 dose,while ensuring the safety and tolerability of the treatment. In this trial, the dose determined to be the maximum tolerated dose will be the recommended phase 2 dose and will be utilized in the cohort expansion.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

In a study of 18 high-risk melanoma patients treated with PEG-IFN-alpha-2a, the most common side effects included myelosuppression (83%), constitutional symptoms (78%), and hepatotoxicity (78%), indicating a significant safety profile that needs consideration.

Compared to low-dose IFN-alpha, PEG-IFN-alpha-2a resulted in higher rates of myelosuppression and liver toxicity, but it caused less fatigue and depression than high-dose IFN-alpha, suggesting it may be a better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and high-risk melanomas. Loquai, C., Nashan, D., Hensen, P., et al.[2018]

In the French SPIRIT trial, a lower dose of pegylated interferon-α-2a (45 μg/week) resulted in significantly less severe hematologic toxicity (27%) compared to the higher dose (90 μg/week) which had a toxicity rate of 54%, leading to fewer treatment discontinuations (10% vs. 40%).

Despite the reduction in dose, the efficacy of pegylated interferon-α-2a combined with imatinib remained comparable, with cumulative molecular response rates showing no significant difference, indicating that 45 μg/week is an effective and safer dosing option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of pegylated interferon-α-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. Johnson-Ansah, H., Guilhot, J., Rousselot, P., et al.[2018]

In a study of 17 early-stage primary myelofibrosis patients treated with recombinant interferon-α, over 80% experienced clinical benefit or stability, indicating its potential efficacy in this condition.

The treatment was well-tolerated, with acceptable toxicity levels, and some patients showed improvement in bone marrow morphology, suggesting that interferon-α may help reverse disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. Silver, RT., Vandris, K., Goldman, JJ.[2022]

In a study of 107 patients with chronic myeloproliferative neoplasms, peginterferon-α2b treatment resulted in high hematological remission rates (86% for essential thrombocythemia and 78% for polycythemia vera) after at least 12 months of therapy.

The treatment was associated with a significant reduction in spleen size and symptoms, with only mild adverse reactions reported (2.8% incidence of thrombotic events), indicating it is a safe and effective option for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms]. Luo, D., Luo, J., Liang, H., et al.[2023]

Pegylated interferons, recently approved for hepatitis C treatment, have a safety profile similar to non-pegylated interferon, but caution is warranted.

Two patients experienced worsening liver disease after receiving pegylated interferon alfa-2b, highlighting the need for careful monitoring of patients undergoing treatment with these new formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse response to pegylated interferon therapy in two patients with chronic hepatitis C. Thomas, WL., Ramos, F., Hospenthal, DR.[2018]

In a phase I study involving 27 patients with advanced renal cell carcinoma, pegylated interferon alfa-2a (PEG-IFN) demonstrated a maximum-tolerated dose of 540 microg/week, with a manageable side-effect profile primarily consisting of mild to moderate symptoms like fatigue and headache.

PEG-IFN showed promising pharmacokinetic properties, achieving steady-state concentrations within 5 weeks and inducing immunologic markers, suggesting it may offer enhanced efficacy and convenience over traditional interferon treatments for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. Motzer, RJ., Rakhit, A., Ginsberg, M., et al.[2018]

In a study of 25 patients with myeloproliferative diseases treated with pegylated interferon alpha-2b, 8 out of 15 patients with the JAK2(V617F) mutation achieved hematological complete remission after 24 months.

Among the JAK2-positive patients in remission, 5 showed a significant reduction in the percentage of JAK2(V617F) cells, indicating that pegylated interferon alpha-2b may effectively target and reduce the mutated cells associated with their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited effects on JAK2 mutational status after pegylated interferon alpha-2b therapy in polycythemia vera and essential thrombocythemia. Samuelsson, J., Mutschler, M., Birgegård, G., et al.[2018]

In a phase 2 trial involving 83 patients with essential thrombocythemia (ET) and polycythemia vera (PV), pegylated interferon alfa-2a (PEG-IFN-α-2a) demonstrated significant hematologic and molecular responses, with 93% and 69% of patients achieving these responses, respectively.

Half of the patients analyzed showed a bone marrow response, with 22% achieving a complete response, indicating that PEG-IFN-α-2a can effectively induce complete bone marrow responses in some patients, although the durability of these responses varies and requires further study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Masarova, L., Yin, CC., Cortes, JE., et al.[2022]

In a study of 62 patients with myelofibrosis treated with pegylated-interferon α-2a (Peg-IFNα-2a) over an average of 26 months, 64% of anemic patients achieved complete response, indicating significant efficacy in improving blood counts and reducing symptoms.

The treatment also led to a reduction in splenomegaly in nearly half of the patients and was associated with manageable side effects, primarily mild hematological issues, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pegylated-interferon α-2a in myelofibrosis: a study by the FIM and GEM French cooperative groups. Ianotto, JC., Boyer-Perrard, F., Gyan, E., et al.[2018]

In a study of 75 patients with myeloproliferative neoplasms treated with pegylated interferon alpha 2a, 78.6% showed a complete or partial response, with over 80% of polycythemia vera patients becoming independent of phlebotomy.

The treatment was well-tolerated, with only 2.6% experiencing vascular events and uncommon severe toxicity, indicating that pegylated interferon alpha 2a is a promising option for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated interferon alpha - 2a is clinically effective and tolerable in myeloproliferative neoplasm patients treated off clinical trial. Gowin, K., Jain, T., Kosiorek, H., et al.[2018]

In a long-term study of 62 patients with myelofibrosis treated with pegylated interferon-α2a, nearly half (48.4%) were alive after a median follow-up of 58 months, indicating a potential survival benefit for those with intermediate and high-risk prognostic scores.

The therapy significantly reduced the JAK2V617F allele burden in 58.8% of patients, with some achieving complete molecular response, suggesting that pegylated interferon not only improves survival but also impacts disease markers positively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and pitfalls of pegylated interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of Myeloproliferative neoplasms (FIM) study. Ianotto, JC., Chauveau, A., Boyer-Perrard, F., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5830374/

Benefits and pitfalls of pegylated interferon-α2a therapy in ... In five patients, the transformation to acute myeloid leukemia occurred after discontinuation of pegylated interferon-α2a, at a median of 4.2 years after ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4528/500969/Real-World-Data-on-Safety-and-Efficacy-of

Real World Data on Safety and Efficacy of Pegylated ... 5 patients developed second primary malignancy on PEG IFN. Conclusion: PEG-IFN is a safe and effective cytoreductive agent in all ...

3. vjhemonc.com vjhemonc.com/video/yz28taswb7o-long-term-phase-ii-results-of-pegylated-interferon-treatment-in-et-and-pv/

ASH 2024 | Long-term Phase II results of pegylated interferon ... The study results indicate that the agent is a durable treatment option for patients with these myeloproliferative neoplasms (MPNs).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01259856

NCT01259856 | Randomized Trial of Pegylated Interferon ... The purpose of this study is to look at the effectiveness of giving participants who have been diagnosed with ET or PV one of two different study regimens over ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473912

Pegylated Interferons: Still a Major Player for the Treatment ... Subsequent 5-year follow-up confirmed ongoing superior CHR responses with interferon of 55.8% versus 44% in the standard arm and superior ...