Pilot Study of IGF-Methotrexate Conjugate in the Treatment of Myelodysplastic Syndrome, CMML and Oligoblastic AML
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
The primary objective of this study is to determine the safety and tolerability of utilizing the insulin-like growth factor-1-methotrexate conjugate, 765IGF-MTX for the treatment of advanced, previously treated myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and oligoblastic acute myelogenous leukemia (oligoblastic AML or O-AML), including determining the maximum tolerated dose (MTD).
详细描述
This pilot study will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal. Assessment of response will be confirmed by bone marrow studies performed at the end of cycles 2, 4, and 6 (each +/- 3 days).
Pharmacokinetics will be performed before and for up to 24 hours after drug administration on days 1 (for 24 hrs) and 15 (for 24 hrs) of cycle 1. Pharmacodynamic samples will be assessed pre-dosing on day 1 of cycle 1, pre-dosing on days 1 and 15 of cycle 2, and pre-dosing on day 15 of cycles 4 and 6.
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
- •Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
- •Confirmed histologic diagnosis on bone marrow biopsy and aspirate within 28 days of trial entry prior to starting cycle
- •Platelets > 10 x 10^9/L
- •ECOG performance status of 0, 1 or 2
- •Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate > 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.
- •Patient must have recovered from the acute toxic effects (≤ grade 1 CTCAE v.4.0) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted
- •Adequate organ function within 14 days of study registration
- •Negative serum pregnancy test in females. Male and female patients with reproductive potential must use an approved contraceptive method if appropriate
排除标准
- •ECOG PS >
- •Patients with active extramedullary disease.
- •Pleural effusions or ascites.
- •Grade 3 peripheral neuropathy within 14 days before enrollment.
- •Active uncontrolled infection or severe systemic infection (enrollment is possible after control of infection).
- •Myocardial infarction within ONE months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
- •Pregnant or breastfeeding - methotrexate is Pregnancy Category X - has been reported to cause fetal death and/or congenital abnormalities. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 10% in patients with a prior history of diabetes, prior to study enrollment.
- •Serious concomitant systemic disorders (e.g., active uncontrolled infection or uncontrolled diabetes) or psychiatric disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
- •Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- •Any history of epilepsy or a seizure disorder or any known prior seizures.
- •Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate.
研究组 & 干预措施
IGF/MTX
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
干预措施: IGF/MTX (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.
Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.
次要结局
- Response Criteria for AML, Complete Remission (CR)(Assessed after 2 cycles of 28 days each.)
- Response Criteria for MDS, Disease Progression, Hgb(Assessed after 2 cycles of 28 days each.)
- Response Criteria for AML, CR With Incomplete Recovery(Assessed after 2 cycles of 28 days each.)
- Response Criteria for MDS, Disease Progression, Blasts Measurements(Assessed after 2 cycles of 28 days each.)
- Response Criteria for MDS, Survival, Death(All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.)
- Response Criteria for AML, Relapse.(Assessed after 6 cycles of 28 days each.)
- Response Criteria for MDS, Complete Remission (CR)(Assessed after 6 cycles of 28 days each.)
- Response Criteria for MDS, Marrow CR(Assessed after 2 cycles of 28 days each.)
- Response Criteria for MDS, Stable Disease(Assessed after 6 cycles of 28 days each. Both patients had at least stable disease for at least 6 cycles.)
- Response Criteria for MDS, Failure(Assessed after 6 cycles of 28 days each.)
- Response Criteria for MDS, Disease Progression, Neutrophils(Assessed after 2 cycles of 28 days each.)