NCT01204164已完成1 期
Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Advanced Hematological Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 9
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
This is a multicenter, open-label, dose escalation Phase 1 study.
详细描述
This is a multicenter, open-label, dose escalation, Phase 1/1b study.
For Parts 1, 2, and 3 of the study, the primary objective is to determine the highest dose of TG02 citrate that can safely be given to patients with different types of hematological malignancy.
For Part 4, the primary objective is to evaluate the safety and tolerability of once-weekly dosing at the maximum-tolerated dose/ Recommended Phase 2 Dose of TG02 in combination with carfilzomib.
This study consists of four parts:
- Part 1: single agent TG02 in acute leukemia patients
- Part 2: single agent TG02 in multiple myeloma patients
- Part 3: TG02 in combination with carfilzomib in multiple myeloma patients
- Part 4: TG02 in combination with carfilzomib in carfilzomib refractory multiple myeloma patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Relapsed AML, ALL, CML in blast crisis, or MDS
- •65+ yrs with AML not eligible for standard frontline chemo
- •Interval from prior treatment to time of study drug at least 5 half-lives for cytotoxic/ noncytotoxic agents.
- •Persistent clinically significant toxicities from prior chemo ≤ Grd 1
- •ECOG PS 0-2
- •Lab values:
- •Cr ≤ 2X ULN
- •ALT and/or AST ≤2.5 X ULN
- •Total bilirubin ≤1.5 X ULN unless considered due to Gilbert's syndrome
- •Negative pregnancy test
- •Can take oral med
- •Part 2 Inclusion Criteria:
- •Relapsed multiple myeloma. At least ≥1 line of therapy and progressed after ≥1 prior therapy
- •Measurable disease defined as at least one of the following:
- •Serum M ≥500 mg/dL
- •Urine M ≥200 mg per 24hr
- •Involved FLC ≥10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
- •Measurable soft tissue plasmacytoma
- •Persistent clinically significant toxicities from prior chemo ≤ Grd 1
- •ECOG PS 0-2
- •Lab values:
- •ANC of >1000/mm3
- •Platelets ≥50,000/mm3
- •Cr ≤2X the ULN
- •ALT and/or AST ≤2.5X ULN
- •Total bilirubin ≤1.5X ULN, unless considered due to Gilbert's syndrome
- •Negative pregnancy test
- •Can take oral med
- •Part 3 Inclusion Criteria:
- •Measurable disease defined as at least one of the following:
- •Serum M ≥500 mg/dL
- •Urine M protein ≥200 mg per 24hr
- •Involved FLC level ≥10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
- •Meet at least one of the criteria below:
- •a. ≥2 prior therapies including proteasome inhibitor and immunomodulatory agent (IMiD)
- •b. ≥1 prior therapy and one of the following abnormalities: 17p del, p53, 1q amp, 1p del, t(4;14)
- •Interval from prior treatment to time of study drug at least 5 half-lives or 3 wks, which ever is shorter, for noncytotoxic agents
- •Persistent clinically significant toxicities from prior chemo ≤ Grd 1 or Grd 2 neuropathy without pain
- •ECOG PS 0-2
- •Lab values:
- •ANC of >1000/mm3 independent of G-CSF
- •Platelets ≥50,000/mm3 independent of transfusion
- •MDRD calculated or measured CrCl of ≥30 mL/min
- •ALT and/or AST ≤3X ULN
- •Total bilirubin ≤2X ULN, unless considered due to Gilbert's syndrome
- •Negative pregnancy test
- •Can take oral med
- •Part 4 Inclusion Criteria:
- •Measurable disease defined as at least one of the following:
- •Serum M ≥500 mg/dL
- 另有 18 项未显示
排除标准
- •Previous allogenic hematopoietic transplant within 90 d
- •Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study
- •Prolonged QTC interval >450ms
- •Symptomatic CNS metastases
- •Known HIV or AIDS
- •Actively treated for a second malignancy
- •Pregnant or nursing women
- •Part 3 Exclusion Criteria:
- •Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
- •Corticosteroids discontinued ≥7 days of initiating therapy
- •Previous chemo within 2 wks
- •Hx of ventricular arrhythmia or symptomatic conduction abnormality within 12m
- •CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, myocardial infarction within 6m
- •Prolonged QTc interval (males >450ms, females >470ms)
- •Previous allogeneic hematopoietic transplant within 90 days of study enrollment, Active GVHD requiring treatment.
- •Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study
- •Symptomatic CNS metastases
- •Known HIV or AIDS
- •Prior or 2nd malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/ml), or other cancer for which the subject has received curative therapy at least 3 yrs prior to study entry
- •Treatment-related MDS
- •Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
- •Primary AL amyloidosis
- •Pleural effusions requiring thoracentesis or ascites requiring paracentesis
- •Pregnant or nursing women
- •Part 4 Exclusion Criteria:
- •Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
- •Previous chemo within 2 wks
- •Hx ventricular arrhythmia or symptomatic conduction abnormality within 12m
- •CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, and myocardial infarction within 6m
- •Prolonged QTc interval (males >450ms, females >470ms)
- •Previous allogeneic hematopoietic transplant within 90 days. Active GVHD requiring treatment
- •Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete study
- •Symptomatic CNS metastases
- •Known HIV or AIDS
- •Prior or 2nd malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/ml), or other cancer for which the subject has received curative therapy at least 3 yrs prior to study entry
- •Treatment-related MDS
- •Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
- •Primary AL amyloidosis
- •Pleural effusions requiring thoracentesis or ascites requiring paracentesis
- •Pregnant or nursing women
研究组 & 干预措施
TG02 in AL
Experimental
Single agent TG02 citrate in acute leukemia patients
干预措施: TG02 citrate (Drug)
TG02 in MM
Experimental
Single Agent TG02 citrate in multiple myeloma patients
干预措施: TG02 citrate (Drug)
TG02 + CFZ in MM
Experimental
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
干预措施: TG02 citrate (Drug)
TG02 + CFZ in MM
Experimental
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
干预措施: Carfilzomib (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
Experimental
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
干预措施: TG02 citrate (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
Experimental
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
干预措施: Carfilzomib (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
Experimental
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 28 days
Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.
次要结局
- Safety(28 days)
- Pharmacokinetics of TG02(28 days)
- Clinical Benefit Response(28 days)
- Overall Response Rate(28 days)
- Progression-Free Survival(28 days)
- Overall Survival(28 days)
- Duration of Response(28 days)
- Pharmacodynamics(28 days)
研究者
研究点 (9)
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