Combination of Pioglitazone and Tyrosine Kinase Inhibitor (TKI) in Relapsed Chronic Myeloid Leukemia Following a First TKI Discontinuation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs), Graded According to Common Terminology Criteria for Adverse Events Version 4.03
研究概览
简要总结
This phase II trial studies how well pioglitazone hydrochloride and tyrosine kinase inhibitor (TKI) therapy works in treating patients with chronic myeloid leukemia (CML) that has come back after a period of improvement (relapsed) after a first TKI discontinuation. TKI may stop the growth of cancer cells by blocking certain enzymes need for cell growth. Although TKI therapies are effective against CML, there are residual cancer cells called leukemia stem cells that are able to hide from TKIs. Pioglitazone is a drug approved by the Food and Drug Administration to treat diabetes and has been shown in laboratory studies to increase CML stem cell death when given together with TKI therapy. Giving pioglitazone with TKI therapy may be effective in treating patients with CML.
详细描述
PRIMARY OBJECTIVES:
I. To assess safety of the combination of pioglitazone (PIO) and TKI in CML subjects who experience a loss of major molecular response (MMR) following a first TKI discontinuation.
II. To assess survival without loss of MMR following a second TKI discontinuation in subjects who achieve or maintain < molecular response (MR)^4.5 with the combination PIO and TKI administered for at least 6 months.
OUTLINE:
Patients receive pioglitazone orally (PO) once daily (QD) on days 1-28. Patients also start or continue the same TKI therapy at the pre-discontinuation doses. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic myeloid leukemia (CML) in any phase
- •Philadelphia chromosome positive acute lymphoblastic leukemia
- •Loss of major molecular response (MMR) following a first TKI discontinuation trial
- •Serum bilirubin < 1.5 x upper limit of normal values
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal values
- •Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period; women of child bearing potential must have a negative urine pregnancy test at the time of enrollment; acceptable methods of birth control include oral contraceptive, intrauterine device, transdermal/implanted or injected contraceptives and abstinence
- •Males must agree to abstain from sexual activity or agree to utilize a medically-approved contraception method during and for 3 months after the treatment period
- •Patient requiring anti-diabetic medications to manage hyperglycemia are eligible. Adjustments of other anti-diabetic agents will be made with close monitoring of blood glucose
- •Informed consent
- •Be able and willing to comply with study visits and procedures
排除标准
- •Known loss of complete cytogenetic response (CCyR) by marrow cytogenetic or blood fluorescence in situ hybridization (FISH) for breakpoint cluster region (BCR)- v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1)
- •Loss of complete hematologic response (CHR)
- •Participation in another clinical trial with any investigative drug within 30 days prior to study enrollment
- •Chronic graft-versus-host disease requiring systemic immunosuppression post-allogeneic hematopoietic stem cell transplantation
- •Cardiovascular disease: history of congestive heart failure, myocardial infarction in the 6 months preceding study entry, symptomatic cardiac arrhythmia requiring treatment
- •History of bladder cancer
- •Gross (visible) hematuria
- •Known history of osteoporosis
- •Known history of macular edema
- •Known history of ABL1-domain mutation that predicts resistance to the discontinued TKI
- •Significant medical or psychiatric disorder that would interfere with consent, study participation, or follow-up
- •Known allergy to pioglitazone
- •Pregnant or breastfeeding
- •Use of thiazolidinedione (TZD) within 28 days prior to enrollment
- •Significant gastrointestinal condition that could potentially impair the absorption or disposition of the drug
- •Uncontrolled peripheral edema (2+ or more) of any etiology
- •Active cancer that requires therapy in the form of chemotherapy or radiation
研究组 & 干预措施
Pioglitazone & TKI therapy
Patients receive pioglitazone PO QD on days 1-28. Patients also start or continue the same tyrosine kinase inhibitor (TKI) therapy at the pre-discontinuation doses. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
干预措施: Pioglitazone (Drug)
Pioglitazone & TKI therapy
Patients receive pioglitazone PO QD on days 1-28. Patients also start or continue the same tyrosine kinase inhibitor (TKI) therapy at the pre-discontinuation doses. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
干预措施: Tyrosine Kinase Inhibitor (TKI) (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs), Graded According to Common Terminology Criteria for Adverse Events Version 4.03
时间窗: Up to 30 days after the end of treatment
The AE incidence will be described. An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. AEs will be assessed through scheduled assessments and subject reported diaries.
Proportion of Subjects Who Achieve and Maintain Major Molecular Response (MMR) Following a Second Discontinuation of TKI Using Blood Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) for Breakpoint Cluster Region-Abelson1 (BCR-ABL1)
时间窗: Up to 6 months
The proportion of subjects that has reappearance of BCR-ABL1 will be described. Descriptive statistics that will summarize the changes in BCR-ABL1 testing over time will be presented. Subgroup analyses will be performed by baseline potential prognostic factors. Subgroups will include: age, gender, race, underlying diagnosis, and other disease-related prognostic factors (disease status).
次要结局
- Proportion of Subjects Who Lose MMR Following Discontinuation of Pioglitazone and TKI Using Blood qRT-PCR for BCR-ABL1(Up to 3 years)
研究者
William Blum
Principal Investigator
Emory University