Phase I/II Study of Plerixafor and Clofarabine in Previously Untreated Older (>/=60 Years) Adult Patients With Acute Myelogenous Leukemia (AML) With Two or More Unfavorable Prognostic Factors for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Participants in Phase I With First Cycle Dose Limiting Toxicities (DLT) Observed
研究概览
简要总结
The goal of Part 1 of this clinical research study is to learn about the safety of the combination of plerixafor and clofarabine when given to patients with previously untreated AML who are at least 60 years old.
The goal of Part 2 of this study is to learn if the combination of plerixafor and clofarabine can help to control previously untreated AML in patients who are at least 60 years old. Study was closed early and did not progress to Part 2.
详细描述
The Study Drugs:
Plerixafor is designed to block a protein on cancer cells from attaching to cells in the bone marrow. This may allow cells in the bone marrow to be more effectively treated by chemotherapy.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 3 groups of up to 6 participants will be enrolled in the Part 1 portion of the study, and up to 48 participants will be enrolled in Part 2.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >/= 60 years
- •Diagnosis of untreated AML (de novo, secondary, or with an antecedent hematologic disorder [AHD]) according to the World Health Organization (WHO) criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •At least 2 of the following adverse prognostic factors: Age >/= 70 years; or AHD; or ECOG performance status of = 2; or intermediate or unfavorable (ie, adverse) karyotype defined as any cytogenetic profile except the presence of any of the following: t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22), t(15;17)(q22;q12) and variants.
- •Provide signed, written informed consent.
- •Be able to comply with study procedures and follow-up examinations.
- •Adequate renal and hepatic function as indicated by all of the following: Total bilirubin </=1.5 x institutional Upper Limit of Normal (ULN); an Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) </=2.5 x Upper limits of normal (ULN); and an estimated creatinine clearance (CrCl) of > 50 mL/min, as calculated by the Cockcroft -Gault equation.
- •Adequate cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) >/=40% on multigated acquisition (MUGA) scan or similar radionuclide angiographic scan; or Left ventricular fractional fractional shortening >/=22% on echocardiography exam; or LVEF >/=40% on echocardiography exam.
- •Women of child-bearing potential (WOCBP) must agree to use adequate birth control through the end of the last treatment visit. WOCBP is a women who has not been naturally postmenopausal for at least 12 consecutive months or who had not undergone previous surgical sterilization.
排除标准
- •Diagnosis of acute promyelocytic leukemia (APL), (French-American-British classification M3 or WHO classification of APL with t(15;17)(q22;q12), (PML/RAR alpha fusion gene and variants).
- •Prior treatment with clofarabine.
- •Prior treatment for AML or an AHD (excluding supportive care, hydroxyurea, hematopoietic cytokines, or lenalidomide [the latter specifically for an AHD only]). Hematopoietic cytokines and lenalidomide must not have been received within 14 days prior to first dose of study drug; hydroxyurea is allowed on study to control white blood cell count (WBC) counts. If any of the above treatments have been received for AML or an AHD within the permissible time periods, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
- •Prior hematopoietic stem cell transplant (HSCT).
- •Prior external beam radiation therapy to the pelvis.
- •Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
- •Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- •Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with clofarabine.
- •Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)
- •Prior positive test for the human immunodeficiency virus (HIV).
- •WBC >50 × 10^9/L; the first 3 patients enrolled on the study will be required to have a WBC of <20 × 10^9/L.
- •Have psychiatric disorders that would interfere with consent, study participation, or follow-up.
- •Have been diagnosed with another malignancy, unless the patient has been disease free for at least 5 years following curative intent therapy, following exceptions: Patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of disease-free duration, if definitive treatment for the condition has been completed or patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or radical prostatectomy has been performed.
- •Are pregnant or lactating.
研究组 & 干预措施
Plerixafor 240 mcg/kg + Clofarabine
Plerixafor 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).
Phase II: Plerixafor at the highest dose tolerated in Phase I.
Plerixafor was dose-escalated in a 3+3 design, starting at 240 mcg/kg, and proceeding to dose levels of 320 mcg/kg, and 400 mcg/kg.
干预措施: Plerixafor (Drug)
Plerixafor 240 mcg/kg + Clofarabine
Plerixafor 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before hour IV administration of Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).
Phase II: Plerixafor at the highest dose tolerated in Phase I.
Plerixafor was dose-escalated in a 3+3 design, starting at 240 mcg/kg, and proceeding to dose levels of 320 mcg/kg, and 400 mcg/kg.
干预措施: Clofarabine (Drug)
结局指标
主要结局
Number of Participants in Phase I With First Cycle Dose Limiting Toxicities (DLT) Observed
时间窗: First cycle of treatment, i.e. first 4 weeks on study
Dose limiting toxicity (DLT) consists of participants who developed DLT during maximum tolerated dose (MTD) estimation period where DLTs observed during dose escalation were used to develop MTD. The MTD is the highest dose level in which \<2 participants of 6 develop first cycle. DLT. Toxicity graded according to the NCI Common Toxicity Criteria Version 3.0. The timeframe to assess dose-limiting toxicities (DLT's) will be the first cycle of treatment, i.e. the first 4 weeks on study. The Plerixafor dose to be used in Phase II of the protocol is the highest dose at which no more than 1 of 6 patients experience a DLT in the Phase I part of the protocol or a lower dose selected at the end of dose escalation.
次要结局
- Participants' Response During First Part of Study(Assessments following 3 cycles (at 12 weeks) up to 5 cycles (20 weeks))
- Number of Participants With Overall Response During Second Part of Study(Continuously monitored, assessments at 12 weeks)