A Phase 1 Trial of Calaspargase Pegol-mknl in Combination With High Dose Cytarabine and Idarubicin in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Primary Outcome Measure
研究概览
简要总结
Characterizing the regimen limiting toxicity (RLT) of chemotherapeutic drug Calaspargase Pegol-mknl as remission induction and consolidation chemotherapy in patients with newly diagnosed Acute Myeloid Leukemia (AML) and Identifying the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Calaspargase Pegol-mknl.
详细描述
This is a single center, non-randomized, open-label, phase I study evaluating regimen-limiting toxicities of Calaspargase Pegol-mknl administered intravenously in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML).
The trial will consist of the induction and consolidation phases of therapy. At the induction phase ( it usually lasts for 29 days): a high-dose of Cytarabine will be administered IV for six doses, plus Idarubicin administered IV for three doses and Calaspargase Pegol-mknl administered IV one dose, using a dose-escalation scheme. At the consolidation phase (single cycle of consolidation lasts 4-8 weeks): a high-dose of Cytarabine will be administered IV for six doses, and Calaspargase Pegol-mknl administered IV for one dose, using a dose-escalation scheme.
The FDA (The US Food and Drug Administration) has not approved Calaspargase Pegol-mknl for Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A histologically or pathologically confirmed diagnosis of AML based on WHO classification. Patients with myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) evolving into AML who are candidates for AML induction therapy are eligible for enrollment.
- •Age 18-65 years old.
- •ECOG performance status <
- •Patients must have normal organ function as defined below:
- •Total bilirubin ≤2X the institutional upper limit of normal (ULN) (except in patients with leukemic infiltration of the liver)
- •AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of the liver)
- •Creatinine Clearance (CrCl) ≥ 40 mL/min (except in patients with evidence of tumor lysis syndrome)
- •Left ventricular ejection fraction (LVEF) ≥50%
- •Female patients of childbearing potential must have a negative pregnancy test <1 week before enrollment. Female patients of childbearing potential who are sexually active and male patients who are sexually active and have female partners of childbearing potential must agree to use a highly effective method of non-hormonal contraception. Contraception should be used during treatment and for at least 3 months after the last dose of Calaspargase pegol-mknl.
- •Ability to understand and willingness to sign a written informed consent document.
- •Agree to comply with the study requirements and agrees to come to the clinic/hospital for required study visits
排除标准
- •Patients with the following clinical histories are excluded:
- •severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis as defined by lipase elevation >5X ULN and with signs or symptoms
- •unprovoked DVT
- •serious or life-threatening thrombosis in any location of the body
- •hemorrhagic or thromboembolic stroke
- •major hemorrhagic event within three weeks before signing ICF; hemorrhage due to thrombocytopenia from underlying AML is excluded
- •patients with hemorrhagic diathesis
- •neurologic/cerebellar disorders that may confound the toxicity monitoring of HiDAC
- •history of serious hypersensitivity reactions to pegylated L-asparaginase therapy
- •Patients receiving any other investigational agents or concurrent chemotherapy or immunotherapy. Hydroxyurea for blast count control is permitted before starting treatment and up to a maximum of 10 days after starting treatment on the study.
- •Patients with AML with any of the following cytogenetic abnormalities: t(15;17), t(8;21), inv(16), t(16;16).
- •Pregnant women and female patients who are lactating and do not agree to stop breast-feeding.
- •Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements
研究组 & 干预措施
Calaspargase pegol-mknl dose level 1
Induction Phase (It usually lasts 29 days):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine.
- The subject will take a dose of 750 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle).
Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take a dose of 750 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine.
- A single cycle of consolidation may last between 4-8 weeks in duration.
干预措施: Calaspargase pegol-mknl (Drug)
Calaspargase pegol-mknl dose level 2
Induction Phase (It usually lasts 29 days):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine.
- The subject will take a dose of 1,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle).
Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take a dose of 1,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine(every 21 days ( per cycle).
- A single cycle of consolidation may last between 4-8 weeks in duration.
干预措施: Calaspargase pegol-mknl (Drug)
Calaspargase pegol-mknl dose level 3
Induction Phase (It usually lasts 29 days):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High- dose Cytarabine.
- The subject will take a dose of 1,500 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle).
Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take a dose of 1,500 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine.
- A single cycle of consolidation may last between 4-8 weeks in duration.
干预措施: Calaspargase pegol-mknl (Drug)
Calaspargase pegol-mknl dose level 4
Induction Phase (It usually lasts 29 days):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine.
- The subject will take a dose of 2,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle).
Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks):
- The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses.
- The subject will take a dose of 2,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine per cycle.
- A single cycle of consolidation may last between 4-8 weeks in duration.
干预措施: Calaspargase pegol-mknl (Drug)
结局指标
主要结局
Primary Outcome Measure
时间窗: From the first day of treatment until 30 days after receiving Calaspargase Pegol-mknl
1\. Incidence of regimen limiting toxicities (RLTs) and Incidence of treatment-emergent adverse events (TEAE).
次要结局
- 1. CR+CRh+CRi(Within 4-8 weeks following completion of induction regimen and completion of consolidation therapy)
- 6. Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment(Immediately after the intervention)
- 5. Overall survival (OS)(From the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months)
- 4. Event-free survival (EFS).(From the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months)
- 2. The duration of CR/CRh/CRi.(immediately after the intervention)
- 3. Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.(During the intervention)
- 7. Plasma asparagine and glutamine and other amino acids levels at baseline and weekly after administration of Calaspargase pegol-mknl. for four weeks.(At baseline and weekly after administration of Calaspargase pegol-mknl for four weeks)
- 8.Plasma asparaginase activity at baseline and weekly after administration of Calaspargase pegol-mknl for four weeks(At baseline and weekly after administration of Calaspargase pegol-mknl for four weeks)
研究者
Ashkan Emadi, MD PHD
Alexander Bland Osborn Endowed Chair and Distinguished Professor of Medical Oncology
West Virginia University