2024-513956-14-00已完成2 期
MRD-guided treatment with pembrolizumab and azacitidine in NPM1mut AML patients with an imminent hematological relapse (PEMAZA)
Technische Universitaet Dresden9 个研究点 分布在 1 个国家目标入组 28 人开始时间: 2024年10月25日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 9
- 主要终点
- The primary endpoint of the trial will be proportion of event-free patients after 24 weeks of combination treatment (i.e. after up to 6 cycles of AZA for 7 d Q4W and up to 8 PEM infusions Q3W). Events are defined as: (i) First hematologic relapse after start of combined therapy, (ii) Death from any cause, (iii) AML-treatment other than PEM and AZA or HMA only.
研究概览
简要总结
To evaluate the safety and efficacy of pembrolizumab (PEM) when administered in combination with standard azacitidine (AZA) in NPM1mut AML patients with molecular relapse defined by the presence of MRD
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent.
- •Negative pregnancy test in women of childbearing potential (negative urine or serum pregnancy within 3 days prior to receiving study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.9.2 – Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- •Male subjects with procreative capacity must agree to use an adequate method of contraception as outlined in Section 5.9.2 – Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- •Age ≥18 years.
- •Patients with NPM1mut AML in complete morphologic remission after conventional chemotherapy (anthracycline ± cytarabine based).
- •Detectable MRD indicating imminent hematologic relapse (NPM1mut MRD ratio >1%, confirmed by central lab).
- •Patients who are not eligible for immediate alloSCT.
- •Patients who are not eligible to undergo alternative intensive treatment.
- •Intended AZA therapy for molecular relapse.
- •ECOG performance status of 0 or
- •Demonstrate adequate organ function as defined in the table below, all labs should be performed within the screening period.
排除标准
- •Prior alloSCT.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- •Autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Known history of, or any evidence of active, non-infectious pneumonitis.
- •Liver cirrhosis or malignant liver tumor.
- •Known severe congestive heart failure, incidence of clinically unstable cardiac or pulmonary disease.
- •Active infection requiring systemic therapy.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- •Treatment with any investigational drug within 4 weeks to study therapy or less than 5 half-lives preceding the first dose of trial medication, whichever is longer.
- •Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- •Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- •Live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- •Anti-cancer mAb within 4 weeks prior to study day 1 or no recovering (i.e., ≤ Grade 1 or at baseline) from adverse events (AE) due to agents administered more than 4 weeks earlier.
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or no recovering (i.e., ≤ Grade 1 or at baseline) from AE due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Prior treatment with an anti-programmed cell death protein (anti PD-1, anti PD-L1 or anti PD L2 agent).
- •Known hypersensitivity to any of the drugs within this study, their constituents or to drugs with similar chemical structure.
- •Receiving immunosuppressive therapy within 7 days prior to the first dose of trial medication.
- •Known history of active TB (Bacillus Tuberculosis).
- •Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
结局指标
主要结局
The primary endpoint of the trial will be proportion of event-free patients after 24 weeks of combination treatment (i.e. after up to 6 cycles of AZA for 7 d Q4W and up to 8 PEM infusions Q3W). Events are defined as: (i) First hematologic relapse after start of combined therapy, (ii) Death from any cause, (iii) AML-treatment other than PEM and AZA or HMA only.
The primary endpoint of the trial will be proportion of event-free patients after 24 weeks of combination treatment (i.e. after up to 6 cycles of AZA for 7 d Q4W and up to 8 PEM infusions Q3W). Events are defined as: (i) First hematologic relapse after start of combined therapy, (ii) Death from any cause, (iii) AML-treatment other than PEM and AZA or HMA only.
次要结局
- Treatment-related mortality during 24 weeks of combined therapy
- Proportion of event-free patients after 12 weeks of combined therapy
- Overall survival.
- Course of MRD-burden measured as quantitative NPM1/ABL ratio over time
研究者
Dr. Jan Moritz Middeke
Scientific
Technische Universitaet Dresden
研究点 (9)
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