Ropeginterferon Alfa-2b for MDS/MPN Overlap Syndromes, Including CMML and MDS/MPN-RS-T
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Overall response
研究概览
简要总结
This phase II trial tests the safety, best dose, and effectiveness of ropeginterferon alfa-2b for the treatment of patients with myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes and chronic myelomonocytic leukemia. Ropeginterferon alfa-2b is a form of interferon. Interferons are a type of signaling protein normally produced by the body as part of the immune response. Interferons interfere with the division of cancer cells and can slow cancer cell growth. Ropeginterferon alfa-2b is a long-acting form of a type of interferon called interferon alfa-2b. In the body, ropeginterferon alfa-2b causes the production of proteins that modulate the immune system and have anticancer effects.
详细描述
PRIMARY OBJECTIVE:
I. To assess the safety and efficacy (overall response, OR) of ropeginterferon alfa-2b in adult patients with myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndrome.
SECONDARY OBJECTIVES:
I. To evaluate baseline cytogenetics, mutation profile, chronic myelomonocytic leukemia (CMML)-specific prognostic scoring system - molecular (CPSS-Mol) risk.
II. To assess the percentage of patient with hematological response based on 2015 international consortium proposal (ICP) MDS/MPN criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 18 years of age at time of consent
- •Documentation of a diagnosis of MDS/MPN overlap syndrome based on World Health Organization (WHO) 2022 classification, including CMML, MDS/MPN with neutrophilia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), or MDS/MPN, not otherwise specified, by local pathology review, and deemed to potentially benefit from study participation by the investigator
- •Written informed consent obtained from participant or participant's legal representative and ability for participant to comply with the requirements of the study
- •Blast =< 10% by marrow immunohistochemistry stain
- •Platelet count of > 50,000/uL
- •Absolute neutrophils count (ANC) of > 1000/uL
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
- •Serum creatinine =< 2.5 mg/dL
- •Serum direct bilirubin < 2.0 mg/dL
- •Serum transaminase < 2.5 times the upper limit of the normal range (ULN) or < 5 times ULN if the transaminase elevation was deemed related to the MDS/MPN
排除标准
- •Prior therapy with interferon or pegylated interferon product, or azacitidine
- •Spleen overtly enlarged by physical exam (eg. greater than 5 fingerbreadth below costal margin)
- •Other standard (including erythropoietin-stimulating agents [ESA] or luspatercept) or experimental therapy for MDS/MPN within 28 days of starting study therapy with the exception of hydroxyurea, which is allowed to continue up to 28 days after cycle 1 day 1 (C1D1) while on protocol
- •Clinically significant autoimmune disease by investigator assessment, regardless if the autoimmune phenomena is related to MDS/MPN overlap syndrome
- •History of or current clinically relevant depression or anxiety per investigator's judgement. Previous suicidal ideation or attempts are not allowed to participate in interferon (IFN) therapy
- •Evidence of severe retinopathy or clinically relevant ophthalmological disorder
- •History of organ transplant
- •Pregnant or breastfeeding women
- •Active uncontrolled infection with clinical symptoms, e.g., presence of bacteria, fungal, human immunodeficiency virus (HIV), hepatitis B or C
- •Active uncontrolled thromboembolic complications or hemorrhage
- •History of any malignancy within 5 years (except adequately treated non-melanoma skin cancer, prostate cancer status post resection with an undetectable prostate-specific antigen [PSA], curative treated in-situ cancer of the cervix, ductal carcinoma in situ [DCIS] of the breast, stage 1 grade 1 endometrial carcinoma, or other solid tumors including lymphomas curatively treated with no evidence of disease for ≥ 1 year prior to study)
- •Uncontrolled active clinically significant illness that, in the investigator's opinion, may affect the patient's participation in this study
- •Active abuse of alcohol and/or illicit drugs
研究组 & 干预措施
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Computed Tomography (Procedure)
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Questionnaire Administration (Other)
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Ropeginterferon Alfa-2B (Biological)
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Bone Marrow Aspiration (Procedure)
Treatment (ropeginterferon alfa-2b)
Patients receive ropeginterferon alfa-2b SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, CT, and collection of blood samples throughout the trial.
干预措施: Bone Marrow Biopsy (Procedure)
结局指标
主要结局
Overall response
时间窗: Up to 24 months
Will be assessed per the 2015 international consortium proposal (ICP) myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) criteria. Overall response rate is defined as the best objective 2015 ICP MDS/MPN response achieved at any time on study (complete remission, complete cytogenetic remission, partial remission, marrow response or clinical benefit). Will be summarized as proportions with corresponding 95% exact binomial confidence intervals.
Incidence of adverse events
时间窗: Up to 24 months
The incidence of adverse events, both hematological and non-hematological will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be summarized as proportions with corresponding 95% exact binomial confidence intervals.
次要结局
- Cytogenetics(At baseline)
- Mutation profile(At baseline)
- Chronic myelomonocytic leukemia-specific prognostic scoring system - molecular risk(At baseline)
- Clinical benefit(Every 3 cycles (cycle length = 28 days))
- Progression-free survival(From initiation of treatment to disease progression or death, assessed up to 24 months)
- Overall survival(From initiation of treatment to death, assessed up to 24 months)
- Change in mutant allele frequencies(From baseline to every 3rd cycle (cycle length = 28 days))
- Percent change in splenomegaly(Every cycle (for clinical exam) and on day 1 of cycles 4 and 7 and at end of treatment (for computed tomography) (cycle length = 28 days))
- Changes in myeloproliferative neoplasm symptom burden(From baseline to day 1 of cycles 1, 2, and 4, and then every 3 cycles (cycle length = 28 days))
- Time to response(Up to 24 months)
- Duration of response(From date of response to date of first evidence of disease recurrence or treatment failure, assessed up to 24 months)
- Changes in packed red blood cell transfusion burden(Up to 24 months)
- Changes in bone marrow morphology and fibrosis(From baseline to day 1 of cycles 4 and 7 and at end of treatment (cycle length = 28 days))
- Change in cytokine profile(From baseline to weeks 25 and 49)