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

Trial Summary

What is the purpose of this trial?

This is a single site, open-label, dose de-escalation, Phase 1 study of pegylated interferon alfa-2a administered after alloHCT in subjects with primary or secondary myelofibrosis. Part 1 of the study will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the Recommended Phase 2 Dose (RP2D). Once the RP2D is identified, 6 additional patients will be enrolled in the expansion cohort.

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.

What data supports the effectiveness of the drug Pegylated Interferon Alfa-2a for treating myelofibrosis?

Research shows that Pegylated Interferon Alfa-2a can help improve symptoms in myelofibrosis patients, such as reducing spleen size and normalizing blood cell counts. It also appears to increase survival rates in patients with certain risk scores and reduce the burden of a specific genetic mutation (JAK2V617F) in many patients. ^{1 2 3 4 5}

Is Pegylated Interferon Alfa-2a safe for humans?

Pegylated Interferon Alfa-2a has been studied for various conditions, including myelofibrosis and melanoma, and is generally considered to have an acceptable safety profile. Common side effects include mild to moderate blood-related issues and fatigue, while more serious side effects are less common. Monitoring during treatment is recommended to manage any potential adverse effects. ^{1 6 7 8 9}

How does the drug Pegylated Interferon Alfa-2a differ from other treatments for myelofibrosis?

Pegylated Interferon Alfa-2a is unique because it can induce high response rates in myelofibrosis patients, especially in early phases, with acceptable side effects. It works by modulating the immune system and has shown effectiveness in reducing symptoms like splenomegaly (enlarged spleen) and improving blood cell counts. ^{1 3 4 10 11}

Research Team

Sagar A. Patel, MD

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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 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]

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 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 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 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]

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 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 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]

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 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]

References

1. England 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. [2018]

2. Italy 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. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Limited effects on JAK2 mutational status after pegylated interferon alpha-2b therapy in polycythemia vera and essential thrombocythemia. [2018]

6. France pubmed.ncbi.nlm.nih.gov

Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and high-risk melanomas. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Adverse response to pegylated interferon therapy in two patients with chronic hepatitis C. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Pegylated interferon alpha - 2a is clinically effective and tolerable in myeloproliferative neoplasm patients treated off clinical trial. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms]. [2023]

10. United States 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. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. [2018]