Phase 1/Phase 2 Study of IMM01 Combined With Azacitidine in Patients With AML and MDS
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 22
- 主要终点
- Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) of IMM01 combination azacitidine
研究概览
简要总结
This trial is an open-lable , multi-center, Phase 1/Phase 2 study that will evaluate the safety, tolerability, Pharmacokinetics, Pharmacodynamics and and immunogenicity of IMM01 combined with Azacitidine in patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).
详细描述
Main study purpose:
- To evaluate the safety and tolerability of IMM01 combined with Azacitidine in patients with AML and MDS.
- To explore the Maximum Tolerated Dose (MTD) of IMM01 combined with Azacitidine, and determine the phase 2 clinical recommended dose (RP2D) of IMM01 combined with Azacitidine.
Secondary study purpose:
- To evaluate the efficacy of IMM01 combined with Azacitidine in patients with AML and MDS.
- To evaluate the Pharmacokinetics and Pharmacodynamics of IMM01 combined with Azacitidine, in patients with AML and MDS.
Exploratory study purpose:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Voluntary participation and written informed consent.
- •Males and females ≥18 years of age
- •The Eastern Oncology Collaboration (ECOG) Status of ≤2
- •Life expectancy of at least 3 months.
- •Women and men of reproductive age must agree and use effective contraception during the study period and for three months after the last administration of IMM01, and women of reproductive age must have negative pregnancy test results within seven days prior to administration.
- •White blood cell count ≤ 20×10⁹/L before the first treatment of the study drug (treatment with hydroxyurea is permitted, but not within 3 days before the first treatment of the study drug).
- •Bone marrow aspiration and bone marrow biopsy were agreed during screening and treatment.
- •For those who have received previous chemotherapy or targeted drug therapy, the interval between the first drug administration should be more than 2 weeks;Prior treatment with chimeric antigen receptor T cells (CAR T cells) should be discontinued for at least 12 weeks after initial dosing(for Cohort 1 and 2).
- •Non-hematological adverse reactions have been restored to grade 1 and below (NCI-CTC AE v5.0, except residual hair loss effect),in patients with previous chemotherapy and targeted drug therapy. Hematologic adverse reactions recovered to investigatory-determined acceptance of study drug administration (for cohort 1 and 2).
- •Appropriate organ functions.
排除标准
- •Received anti-CD47 antibody or SIRPα fusion protein research drugs.
- •Who has received allogeneic hematopoietic stem cell transplantation and other organ transplants; Autologous hematopoietic stem cell transplantation less than six months.
- •Central nervous system leukemia orcentral nervous system invasion.
- •Developed other malignant tumors within 5 years prior to enrollment.Except:
- •Cured carcinoma in situ and non-melanoma skin cancer of the cervix; Complete remission of disease at least 2 years prior to initial administration and no need for antineoplastic therapy.
- •Patients with a history of active autoimmune diseases;
- •Major surgery within 4 weeks prior to initial treatment;
- •Subjects requiring systemic corticosteroids (equivalent to >10 mg prednisone/day) or other immunosuppressive agents within 14 days prior to initial treatment or during the study period;
- •Hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) or pulmonary hypertension or unstable angina that is also not controlled by medication;
- •Patients with a history of arterial or deep vein thrombosis within the 6 months prior to enrollment, or evidence or history of bleeding tendency within the 2 months prior to enrollment, regardless of severity.
- •Severe gastrointestinal diseases;
- •With acute lung disease, pulmonary fibrosis, Severe dyspnea, lung insufficiency or continuous oxygen inhalation.
- •Patients who have been severely infected within 4 weeks prior to initial administration;
- •Active hepatitis B or hepatitis C ; human immunodeficiency virus (HIV) antibody is positive.
- •Live attenuated vaccine should be administered within 4 weeks prior to initial administration.
- •Patients with a history of severe allergy to protein drugs (CTCAE V5.0 grade > 3); Or the patient is allergic to azacytidine.
- •Participate in clinical trials of other drugs 28 days prior to initial dosing.
- •A history of prior neurological or mental disorders, such as epilepsy, dementia, or alcohol, drug or substance abuse, affects compliance.
- •Other conditions that the investigator considers inappropriate for participation in this clinical trial.
研究组 & 干预措施
Relapse/Refractory AML
IMM01 and Azacitidine in Relapse/Refractory AML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: IMM01 (Drug)
Relapse/Refractory AML
IMM01 and Azacitidine in Relapse/Refractory AML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: Azacitidine (Drug)
Relapsed or Refractory MDS
IMM01 and Azacitidine in Relapse/Refractory MDS
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: IMM01 (Drug)
Relapsed or Refractory MDS
IMM01 and Azacitidine in Relapse/Refractory MDS
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: Azacitidine (Drug)
Treatment naive AML
IMM01 and Azacitidine in treatment naive AML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: IMM01 (Drug)
Treatment naive AML
IMM01 and Azacitidine in treatment naive AML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: Azacitidine (Drug)
Treatment naive MDS and naive CMML
IMM01 and Azacitidine in treatment naive MDS and naive CMML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: IMM01 (Drug)
Treatment naive MDS and naive CMML
IMM01 and Azacitidine in treatment naive MDS and naive CMML
Interventions:
Drug: IMM01 Drug: Azacitidine
干预措施: Azacitidine (Drug)
结局指标
主要结局
Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) of IMM01 combination azacitidine
时间窗: Though end of DLT evaluation period,up to approximately 28 days.
To be summarized using descriptive statistics
Maximum Tolerated Dose (MTD)
时间窗: Dose-limiting toxicities will be evaluated during the first cycle (28 days) of treatment.
MTD is the highest dose in patients with DLT incidence \<1/3.For a dose group to be assessed as MTD, at least 6 DLT data must be available to evaluate the subject.
次要结局
- Pharmacokinetics - AUC(Within 60 minutes prior to infusion on Cycle 1 Day 1, Day 8, Day 15 and Cycle 2-6 Day 1 (28 days cycle).10 minutes post-infusion on Cycle 1 Day 15 and Cycle 6 Day 22 (28 days cycle ) .10 minutes and 4 hours post-infusion on Cycle 1 Day 1 (28 days cycle).)
- Pharmacokinetics - Cmax(Within 60 minutes prior to infusion on Cycle 1 Day 1, Day 8, Day 15 and Cycle 2-6 Day 1 (28 days cycle).10 minutes post-infusion on Cycle 1 Day 15 and Cycle 6 Day 22 (28 days cycle ) .10 minutes and 4 hours post-infusion on Cycle 1 Day 1 (28 days cycle).)
- Pharmacokinetics - tmax(Within 60 minutes prior to infusion on Cycle 1 Day 1, Day 8, Day 15 and Cycle 2-6 Day 1 (28 days cycle).10 minutes post-infusion on Cycle 1 Day 15 and Cycle 6 Day 22 (28 days cycle ) .10 minutes and 4 hours post-infusion on Cycle 1 Day 1 (28 days cycle).)
- Pharmacokinetics - T1/2(Within 60 minutes prior to infusion on Cycle 1 Day 1, Day 8, Day 15 and Cycle 2-6 Day 1 (28 days cycle).10 minutes post-infusion on Cycle 1 Day 15 and Cycle 6 Day 22 (28 days cycle ) .10 minutes and 4 hours post-infusion on Cycle 1 Day 1 (28 days cycle).)
- Response Rate(When the last subject enrolled completes approximately 12 months of treatment)
- Overall Remission (OR):(When the last subject enrolled completes approximately 12 months of treatment)