A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine. (Omacetaxine Mepesuccinate; OMA) in the Treatment of Patients With Chronic Myeloid. Leukemia (CML) Who Have Failed or Are Intolerant to Tyrosine Kinase Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 29
- 主要终点
- Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
研究概览
简要总结
A Phase II open-label trial of subcutaneous HHT (omacetaxine mepesuccinate) in the treatment of patients who are resistant to or intolerant to Tyrosine Kinase Inhibitors.
详细描述
This will be an open label, multicenter study of subcutaneous HHT (omacetaxine mepesuccinate) therapy of patients with chronic myeloid leukemia (CML) in chronic, accelerated, or blast phase who have failed or are intolerant to tyrosine kinase inhibitor therapy. Patients will be treated with induction course cycles consisting of subcutaneous (SC) HHT 1.25 mg/m² twice daily for 14 consecutive days every 28 days. Patients will be evaluated every 7 days with complete blood and platelet counts while undergoing induction therapy; the number of consecutive doses of HHT or intervals between subsequent cycles may be adjusted, as clinically indicated, according to guidelines provided in the treatment plan.
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 patients, age 18 years or older
- •Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
- •Patients will have either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least two tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response).
- •Acceptable Renal and Liver Function
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Sexually active patients and their partners must use an effective double barrier method of contraception
排除标准
- •New York Heart Association classification (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
- •Myocardial infarction in the previous 12 weeks.
- •Other concurrent illness which would preclude study conduct and assessment
- •uncontrolled and active infection, and positive HIV or positive HTLV I/II status, whether on treatment or not.
- •Pregnant or lactating.
- •Any medical or psychiatric condition, which may compromise the ability to give written informed consent or to comply with the study protocol.
- •Lymphoid Ph+ blast crisis
- •Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent
研究组 & 干预措施
OMA
Omacetaxine mepesuccinate (OMA) Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days for up to six cycles.
Omacetaxine mepesuccinate (OMA) Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days for up to 24 months.
干预措施: Omacetaxine mepesuccinate (Drug)
结局指标
主要结局
Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
时间窗: Day 1 up to 6 months
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses. Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last \>= 8 weeks to be considered meaningful. Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population
时间窗: Day 1 up to 9 months
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses. Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful. Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available. Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows \>0% - 35% Ph+ cells. Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total
时间窗: up to 4 years
TEAE are any untoward events that were newly occurring or worsening from Baseline. Treatment related toxicity was considered by the investigator to be unrelated, possibly, probably or unknown related to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence that is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. A participant is only counted once in each category (at worst severity or strongest relationship).
次要结局
- Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS(Day 1 up to Month 6)
- Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL(Day 1 up to Month 6)
- Percentage of Participants in Each Hematologic Response Category(Day 1 up to Month 6)
- Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response(Day 1 up to Month 9)
- Number of Treatment Cycles Needed to Achieve Best Hematologic Response(Day 1 up to Month 6)
- Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)(Day 1 up to Month 9)
- Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL(Day 1 up to Month 9)
- Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response(Day 1 up to Month 9)
- Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response(Day 1 up to Month 6)
- Kaplan-Meier Estimates for Time to Disease Progression(up to 4 years)
- Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response(Day 1 up to Month 9)
- Kaplan-Meier Estimates for Duration of Best Hematologic Response(up to four years)
- Kaplan-Meier Estimates for Duration of Best Cytogenetic Response(up to four years)
- Kaplan-Meier Estimates for Overall Survival(up to 4 years)