Pegylated Interferon Alfa-2a for Myelofibrosis (ATIOM Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Utah
Must not be taking: Investigational agents
Disqualifiers: Graft-versus-host, Cardiovascular disorders, others
No Placebo Group
Approved in 5 jurisdictions
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.
12345Is 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.
16789How 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.
1341011Eligibility 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.Participant Groups
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).
1Treatment groups
Experimental Treatment
Group I: Treatment: All PatientsExperimental Treatment1 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Huntsman Cancer Institute at the University of UtahSalt Lake City, UT
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Who is running the clinical trial?
University of UtahLead Sponsor
References
Efficacy and safety of pegylated-interferon α-2a in myelofibrosis: a study by the FIM and GEM French cooperative groups. [2018]Myeloproliferative neoplasm-related myelofibrosis is associated with cytopenic or proliferative phases, splenomegaly and constitutional symptoms. Few effective treatments are available and small series suggested that interferon could be an option for myelofibrosis therapy. We performed a retrospective study of pegylated-interferon α-2a (Peg-IFNα-2a) therapy in myelofibrosis. Sixty-two patients treated with Peg-IFNα-2a at 17 French and Belgian centres were included. Responses were determined based on the criteria established by the International Working Group for Myelofibrosis Research and Treatment. Mean follow-up was 26 months. Sixteen of 25 anaemic patients (64%) (eight concomitantly receiving recombinant erythropoietin) achieved a complete response and transfusion-independence was obtained in 5/13 patients (38·5%). Constitutional symptoms resolved in 82% of patients. All five leucopenic patients normalized their leucocyte counts, whereas a normal platelet count was obtained in 5/8 thrombocytopenic patients. Splenomegaly was reduced in 46·5% of patients, and complete resolution of thrombocytosis and leucocytosis were observed in 82·8% and 68·8% of patients, respectively. Side effects (mostly haematological) were mainly of grade 1-2. The only factor independently associated with treatment failure was a spleen enlargement of more than 6 cm below the costal margin. In conclusion, Peg-IFNα-2a induced high response rates with acceptable toxicity in a large proportion of patients with primary and secondary myelofibrosis, especially in early phases.
Benefits and pitfalls of pegylated interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of Myeloproliferative neoplasms (FIM) study. [2019]We have previously described the safety and efficacy of pegylated interferon-α2a therapy in a cohort of 62 patients with myeloproliferative neoplasm-associated myelofibrosis followed in centers affiliated to the French Intergroup of Myeloproliferative neoplasms. In this study, we report their long-term outcomes and correlations with mutational patterns of driver and non-driver mutations analyzed by targeted next generation sequencing. The median age at diagnosis was 66 years old, the median follow-up since starting pegylated interferon was 58 months. At the time of analysis, 30 (48.4%) patients were alive including 16 still being treated with pegylated interferon. The median survival of patients with intermediate and high-risk prognostic Lille and dynamic International Prognostic Scoring System scores treated with pegylated interferon was increased in comparison to that of historical cohorts. In addition, overall survival was significantly correlated with the duration of pegylated interferon therapy (70 versus 30 months after 2 years of treatment, P<10-12). JAK2V617F allele burden was decreased by more than 50% in 58.8% of patients and two patients even achieved complete molecular response. Next-generation sequencing analyses performed in 49 patients showed that 28 (57.1%) of them carried non-driver mutations. The presence of at least one additional mutation was associated with a reduction of both overall and leukemia-free survival. These findings in a large series of patients with myelofibrosis suggest that pegylated interferon therapy may provide a survival benefit for patients with intermediate- or high-risk Lille and dynamic International Prognostic Scoring System scores. It also reduced the JAK2V617F allele burden in most patients. These results further support the use of pegylated interferon in selected patients with myelofibrosis.
Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report. [2022]The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in "early" PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 μg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.
Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). [2022]Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients.
Limited effects on JAK2 mutational status after pegylated interferon alpha-2b therapy in polycythemia vera and essential thrombocythemia. [2018]Twenty-five patients with myeloproliferative diseases were treated with pegylated interferon alpha-2b. Prior to therapy, 15/25 patients had a JAK2(V617F) mutation. Eight JAK2-positive patients were on therapy in hematological complete remission at 24 months. Five of eight patients demonstrated a 1.2-3.6 fold reduction in the percentage of JAK2(V617F) cells.
Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and high-risk melanomas. [2018]Pegylated (PEG)-IFN-alpha-2a is a modified form of recombinant human IFN-alpha-2a with sustained absorption and prolonged half-life. Our aim was to evaluate its safety profile in adjuvant treatment of high-risk melanoma patients in a single centre setting and to compare this safety profile with data obtained from the literature for a) low dose IFN-alpha and b) high dose IFN. Eighteen consecutive melanoma patients (AJCC 2002 stages IIa-IIIc) were retrospectively analyzed for toxicities associated with adjuvant PEG-IFN-alpha-2a (180 microg/week s.c.). The most frequently reported adverse events were constitutional side effects (78%), myelosuppression (83%) and hepatotoxicity (78%). The proportion of patients receiving PEG-IFN-alpha-2a and suffering from myelosuppression and liver toxicity was significantly higher than for patients reported in the literature undergoing low-dose IFN-alpha treatment (P = 0.008, P = 0.001 respectively), while fatigue and depression were seen less frequently with PEG-IFN-alpha-2a. By contrast, compared to patients treated with high-dose IFN-alpha, PEG-IFN-alpha-2a treated patients less frequently experienced fatigue (P
Adverse response to pegylated interferon therapy in two patients with chronic hepatitis C. [2018]Pegylated interferons have recently been approved for treatment of hepatitis C. The safety of these formulations is reported to be similar to that of non-pegylated interferon. We present two patients who experienced exacerbations of their liver disease following administration of pegylated interferon alfa-2b. Vigilant monitoring of patients treated with these new agents is recommended.
Pegylated interferon alpha - 2a is clinically effective and tolerable in myeloproliferative neoplasm patients treated off clinical trial. [2018]Polycythemia vera, essential thrombocytosis, and myelofibrosis are chronic Philadelphia-negative myeloproliferative neoplasms that are characterized by clonal hematopoiesis, splenomegaly, risk of hemorrhagic and thrombotic sequelae, and profound symptom burden. We review the outcomes of 75 myeloproliferative neoplasm patients treated with pegylated interferon alpha 2a off study at an academic medical center. In the 56 treated polycythemia vera and essential thrombocytosis patients, a complete or partial response was obtained in 78.6% of patients per ELN/IWG-MRT revised criteria, with >80% of polycythemia vera patients becoming phlebotomy independent and 60% of essential thrombocytosis patients having platelet normalization with therapy. In the 19 treated myelofibrosis patients, stable disease was seen in 63.2% of patients. Vascular events occurred in 2/75 (2.6%) of treated patients while on therapy. Grade 3 toxicity was uncommon with leukopenia noted in 1 patient (1.3%). The most common adverse event overall was grade 1 fatigue in 18.7%. This retrospective single center analysis demonstrates pegylated interferon alpha 2a is active and well-tolerated therapy outside the support of a clinical trial. These results substantiate the previously reported efficacy of pegylated interferon alpha 2a in myeloproliferative neoplasms. Further prospective and randomized clinical trial data is required to better delineate pegylated interferon alpha 2a's use in myeloproliferative disease, with emphasis placed on comprehensive molecular characterization, allelic burden quantification, and measurement of histologic response.
[Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms]. [2023]To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).
Tolerability and efficacy of pegylated interferon-α-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. [2018]The pegylated form of interferon-α-2a (PegIFNa2a) in combination with imatinib has demonstrated a molecular improvement in patients with chronic-phase chronic myeloid leukemia. However, to the authors' knowledge, the appropriate dose of PegIFNa2a has not been established to date.
Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. [2018]Pegylated (40 kd) interferon alfa-2a (IFNalpha2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNalpha2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC).