Prospective Evaluation of Ruxolitinib Efficacy for CNL/aCML Patients With Mutation of CSF3R
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 7
- 主要终点
- Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR))
研究概览
简要总结
This phase II trial studies how well ruxolitinib phosphate works in treating patients with chronic neutrophilic leukemia (CNL) or atypical chronic myeloid leukemia (aCML). Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cells to reproduce. This trial also studies the genetic makeup of patients. Certain genes in cancer cells may determine how the cancer grows or spreads and how it may respond to different drugs. Studying how the genes associated with CNL and aCML respond to the study drug may help doctors learn more about CNL and aCML and improve the treatment for these diseases.
详细描述
PRIMARY OBJECTIVES:
I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response, partial [CRp]).
SECONDARY OBJECTIVES:
I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib.
II. To determine whether hematologic responses correlate with certain types of mutations in colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in the peripheral blood.
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
- •Subjects must be newly diagnosed or previously diagnosed with CNL or aCML; all patients must have a bone marrow biopsy completed during the screening or baseline period if one has not been done within 90 days of day 1, cycle one
- •Subjects must have platelet count greater than 25,000 per microliter at baseline and at the start of study (day 1, cycle 1) visit
- •Subjects must be able to discontinue any drug treatment aimed at lowering disease burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs that have more long-lasting effects on the marrow, such as thalidomide and its analogs, and interferon, subjects should discontinue these no later than day -28
- •Subjects must be willing to accept/continue transfusions to treat low hemoglobin levels
- •Subjects must have a life expectancy of > 6 months
排除标准
- •Subjects unable to review and sign informed consent form
- •Females who are pregnant or breastfeeding, and males and females who cannot comply with requirements to avoid fathering a child or becoming pregnant
- •Subjects with known diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C; viral testing is not required; subjects with a history of Hepatitis B and/or C are allowed on trial if the virus is undetected at the time of enrollment
- •Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin 4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)
- •Subjects with end stage renal function (creatinine clearance [CrCl] < 15 mL/min or glomerular filtration rate [GFR] <15 mL/min) regardless of whether hemodialysis is required
- •Subjects with clinically serious infections requiring ongoing antibiotic therapy
- •Subjects with severe (immediately life threatening) and recent (occurring within the last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study participation
- •Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies (aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below 50,000 on two different laboratory evaluations, separated by minimum of two weeks
- •Taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy other than those therapies permitted
- •Subjects with invasive malignancy over the previous 2 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers
- •Previous allergic reactions to janus kinase (JAK) inhibitors or excipients
- •Prior therapy with ruxolitinib or other JAK inhibitors
- •Subjects who have had major surgery within 4 weeks prior to entering the study
- •Subjects who are anticipated to receive a transplant within the first 6 months of treatment on trial
研究组 & 干预措施
Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
干预措施: Quality-of-Life Assessment (Other)
Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
干预措施: Questionnaire Administration (Other)
Treatment (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.
干预措施: Ruxolitinib Phosphate (Drug)
结局指标
主要结局
Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR))
时间窗: Start of cycle 7
A subject is defined as being responsive (responder) if he or she has achieved complete response (CR) or partial response (PR) at the beginning of cycle 7 compared to start of study (day 1,cycle 1). Subjects who do not reach the start of cycle 7 are counted as non-responders. Proportions with 95% exact confidence intervals will be computed. Protocol-defined Response evaluates changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table). IWG-defined Response evaluates bone marrow cellularity and myeloblast percent, absence of osteopmyelofibrosis, peripheral blood elements (white blood cell, Neutrophil, Monocyte and platelet counts, hemoglobin density, percent blasts and Neutrophil precursors), symptom resolution, dysplasia, and spleen size to determine response (attached reference).
次要结局
- Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events.(Up to 6 weeks after last dose of ruxolitinib phosphate)
- Percentage of Participants With Early Drop Off (Prior to Completion of Cycle 3)(up to the end of cycle 3 (12 weeks))
- Median Time on Study (Months) for All Enrolled Subjects(Outcome is measured from the first dose of study drug. If study drug continues to be effective, patient may be eligible to continue on study drug past 24 cycles (up to 4.5 years))
- Percentage of Participants Who Reach Cycle 7(Start of cycle 7)
- Percentage of Participants With Early Drop Off (After Completion of Cycle 3 and Prior to Completion of Cycle 6)(Between cycle 3 and cycle 6)
- Maximum Clinical Responses(Up to 6 weeks after last dose of ruxolitinib phosphate)
- Change in Spleen Size, Evaluated by Ultrasound(Measured on Day1 Cycle 1 and Day 1 Cycle 7)
- Change in Symptom Score as Measured by a Modified Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF](Measured at baseline and Day 1 Cycle 7)
- Percentage of Patients Who Achieve Clinical Response of Partial Response or Better by CSF3R Mutation Status(Start of cycle 7)
- Percentage of Participant With Any Hematologic Grade III or IV Adverse Events.(Up to 6 weeks after last dose of ruxolitinib phosphate)
- Overall Survival in All Enrolled Patients(At stem-cell transplantation or up to 5 years after enrollment in the study)
- Percentage of Participants Who Achieved Clinical Response of Partial Response or Better(Start of cycle 7)
- Median Time on Study (Months) for Early Drop Offs(End of cycle 6)
研究者
Kim-Hien Dao
Principal Investigator
OHSU Knight Cancer Institute