A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Response to Treatment
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine and vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell growth. Giving more than one drug (combination chemotherapy) together with decitabine and vorinostat may kill more cancer cells than with chemotherapy alone.
PURPOSE: This phase II trial is studying how well giving decitabine and vorinostat together with combination chemotherapy works in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma that has relapsed or not responded to treatment.
详细描述
OBJECTIVES:
Primary
- Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies. Samples are analyzed for hypermethylation at diagnosis and demethylation post-exposure with decitabine and vorinostat using LINE methylation.
OUTLINE:
Patients receive decitabine IV over 1 hour and oral vorinostat twice daily on days 1-4; vincristine sulfate IV on days 5, 12, 19, and 26; oral prednisone twice daily on days 5-33; doxorubicin hydrochloride IV over 15 minutes and cytarabine intrathecally (IT) on day 5; pegaspargase IV or intramuscularly on days 6, 12, 19, and 26; and methotrexate* IT on days 12 and 33. Patients with Philadelphia chromosome-positive disease may also receive oral imatinib mesylate once daily on days 5-33.
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
- 2 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia with ≥ 5% blasts in the bone marrow (M2/M3) (with or without extramedullary disease) that meets 1 of the following criteria:
- •Refractory disease/induction failure (failure to achieve initial remission after 2 lines of induction therapy)
- •Relapsed disease (in first relapse or higher)
- •Central nervous system (CNS)-positive disease allowed
- •Karnofsky performance status (PS) 50-100% (for patients ≥ 16 years of age) OR Lansky PS 50-100% (for patients < 16 years of age)
- •Life expectancy ≥ 8 weeks
- •Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- •0.4 mg/dL (for patients 1 to 5 months of age)
- •0.5 mg/dL (for patients 6 to 11 months of age)
- •0.6 mg/dL (for patients 1 year of age)
- •0.8 mg/dL (for patients 2 to 5 years of age)
- •1.0 mg/dL (for patients 6 to 9 years of age)
- •1.2 mg/dL (for patients 10 to 12 years of age)
- •1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
- •1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
- •ALT < 5 times upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 times ULN for age
- •LVEF ≥ 40% by ECHO/MUGA scan
- •Shortening fraction > 29% by ECHO/MUGA scan
- •Able to swallow capsules
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 2 months after completion of study treatment
- •No untreated positive blood cultures or progressive infections as assessed by radiographic studies
- •No known allergy to any of the agents or their ingredients used in this study
- •Patients with clinically significant prior allergies to pegaspargase may be treated with asparaginase-Erwinia, if available
- •Patients who cannot receive asparaginase on this study (e.g., due to prior pancreatitis, stroke, or other toxicity) are eligible provided they meet all other inclusion/exclusion criteria
- •Recovered from prior therapy (defined as CTCAE v3.0 toxicity ≤ grade 1)
- •More than 3 weeks since prior chemotherapy for cancer other than hydroxyurea for patients with WBC > 10,000/mm³
- •At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)
- •At least 1 month since prior biologic therapy, such as monoclonal antibodies
- •At least 3 months since prior hematopoietic stem cell transplantation
排除标准
- •Evidence of graft-versus-host disease
- •Concurrent valproic acid
- •Concurrent coumadin/warfarin other than a short course administered in a prophylactic setting
研究组 & 干预措施
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: cytarabine (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: decitabine (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: doxorubicin hydrochloride (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: imatinib mesylate (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: methotrexate (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: pegaspargase (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: prednisone (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: vincristine sulfate (Drug)
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
干预措施: vorinostat (Drug)
结局指标
主要结局
Response to Treatment
时间窗: Day 33
Response includes both complete remission (defined as \<5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
次要结局
- Level of Methylation(Day 33)