A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine (IND# 133688, NSC# 102816) to Chemotherapy in Infants With Acute Lymphoblastic Leukemia (ALL) and KMT2A(MLL) Gene Rearrangement
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 170
- 主要终点
- Tolerability of Azacitidine in Combination With Interfant-06 Standard Chemotherapy in Evaluable Infant Patients With Newly Diagnosed ALL With KMT2A Gene Rearrangement (KMT2A-R). KMT2A Gene Rearrangement (KMT2A-R)
研究概览
简要总结
This pilot phase II trial studies the side effects of azacitidine and combination chemotherapy in infants with acute lymphoblastic leukemia and KMT2A gene rearrangement. Drugs used in chemotherapy, such as methotrexate, prednisolone, daunorubicin hydrochloride, cytarabine, dexamethasone, vincristine sulfate, pegaspargase, hydrocortisone sodium succinate, azacitidine, cyclophosphamide, mercaptopurine, leucovorin calcium, and thioguanine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug may kill more cancer cells.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the tolerability of azacitidine in addition to Interfant-06 standard chemotherapy in infants with newly diagnosed acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement (KMT2A-R).
SECONDARY OBJECTIVE:
I. To evaluate the biologic activity of azacitidine by pharmacodynamic assessment of global deoxyribonucleic acid (DNA) methylation in peripheral blood mononuclear cells (PBMCs) of infants treated with azacitidine.
EXPLORATORY OBJECTIVES:
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
- — 至 364 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants must be > 36 weeks gestational age at the time of enrollment
- •Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia) or acute leukemia of ambiguous lineage (ALUL), which includes mixed phenotype acute leukemia (MPAL); for patients with ALUL, the morphology and immunophenotype must be at least 50% B lymphoblastic
- •Central nervous system (CNS) status must be determined based on a sample obtained prior to the administration of any systemic or intrathecal chemotherapy, with the exception of steroid pretreatment
排除标准
- •Patients with known absence of KMT2A-rearrangement leukemia prior to enrollment
- •Patients with Down syndrome
- •Patients with secondary B acute lymphoblastic leukemia (B-ALL) that developed after treatment of a prior malignancy with cytotoxic chemotherapy
- •With the exception of steroid pretreatment or the administration of intrathecal methotrexate or intrathecal cytarabine, receipt of any other prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL15P1
研究组 & 干预措施
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Azacitidine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Biospecimen Collection (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Computed Tomography (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Cytarabine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Daunorubicin (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Dexamethasone (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Echocardiography (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Hydrocortisone Sodium Succinate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Leucovorin (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Leucovorin Calcium (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Mercaptopurine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Methotrexate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Multigated Acquisition Scan (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Pegaspargase (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Prednisolone (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Thioguanine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
干预措施: Vincristine (Drug)
结局指标
主要结局
Tolerability of Azacitidine in Combination With Interfant-06 Standard Chemotherapy in Evaluable Infant Patients With Newly Diagnosed ALL With KMT2A Gene Rearrangement (KMT2A-R). KMT2A Gene Rearrangement (KMT2A-R)
时间窗: 6 months
Proportion of KMT2A-Rearranged patients treated with azacitidine with Dose Limiting Toxicities (DLTs) from the first course of azacitidine administration up to fourth course of azacitidine administration.
次要结局
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to Second Course of Azacitidine(Week 13, Day 1 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to First Course of Azacitidine(Week 6, Day 1 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of Second Course of Azacitidine(Week 13, Day 5 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of First Course of Azacitidine(Week 6, Day 5 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy))