A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 126
- 主要终点
- Number of Patients Who Demonstrate Complete or Partial Response
研究概览
简要总结
This randomized phase II trial studies how well low-dose lenalidomide works compared with high-dose lenalidomide in treating younger patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas that have come back (recurrent), have not responded to treatment (refractory), or are growing, spreading, or getting worse (progressive). Lenalidomide is classified as an immunomodulatory drug as it boosts the immune system. It has other potential anti-tumor effects, for example, it may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether low-dose lenalidomide is more or less effective than high-dose lenalidomide in treating patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas.
详细描述
PRIMARY OBJECTIVES:
I. To determine the objective response rate in children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with Regimen A low-dose (20 mg/m^2/dose) or Regimen B high-dose (115 mg/m^2/dose) lenalidomide.
SECONDARY OBJECTIVES:
I. To estimate the event-free survival (EFS) (based on standard two-dimensional tumor measurements, determined by each institution) of children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with lenalidomide.
II. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuated inversion recovery [FLAIR], T1-weighted post-contrast).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a body surface area (BSA) >= 0.4 m^2 at the time of study enrollment
- •Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed, progressed, or become refractory to conventional therapy; patients with neurofibromatosis (NF-1) are eligible
- •Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required
- •Patients must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI); for a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (i.e. visible on more than one slice)
- •To document the degree of residual tumor, the following must be obtained:
- •All patients must have a brain MRI with and without contrast (gadolinium) within 1 week prior to study enrollment; for patients on steroids, baseline MRI scans must be performed after at least 1 week at a stable or decreasing dose of steroids
- •All patients with a history of spinal or leptomeningeal disease, and those patients with symptoms suspicious of spinal disease, must have a spine MRI with and without contrast (gadolinium) performed within 2 weeks prior to study enrollment
- •Patients must have a Lansky or Karnofsky performance status score of >= 60%; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- •Patients must have been treated with at least one prior treatment regimen that included carboplatin; patients who have received prior radiation therapy for this tumor are eligible
- •Patients must have recovered (to Common Toxicity Criteria [CTC] version [v.]4.0 =< grade 1 unless indicated below) from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, with the exception of alopecia, weight changes and grade I or II lymphopenia
- •Myelosuppressive chemotherapy: must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea or mitomycin-C)
- •Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
- •Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- •Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- •Radiation therapy (RT): patients must have had their last fraction of craniospinal RT >= 6 months prior to study entry and their last fraction of focal RT >= 4 weeks prior to study entry; if the lesion used for on-study criteria is in the radiation field, there must be evidence of tumor progression after radiation therapy was completed
- •Study specific limitations on prior therapy:
- •Patients who have received thalidomide are eligible if all acute thalidomide-related toxicity has resolved
- •Patients must not have received lenalidomide previously
- •Growth factor(s): must not have received within 2 weeks of entry onto this study
- •Steroids: patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to baseline MRI
- •Peripheral absolute neutrophil count (ANC) >= 1,000/uL
- •Platelet count >= 100,000/uL (transfusion independent)
- •Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/m^2 OR a serum creatinine based on age/gender as follows:
- •0.4 mg/dL (1 month to < 6 months of age)
- •0.5 mg/dL (6 months to < 1 year of age)
- •0.6 mg/dL (1 to < 2 years of age)
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
- •Serum albumin >= 2 g/dL
- •No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical indication for determination
- •Patients must be able to swallow intact capsules
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Female patients who are pregnant are not eligible
- •Lactating females are not eligible unless they have agreed not to breastfeed their infants while receiving protocol therapy and for 28 days after the last dose of lenalidomide
- •Female patients of childbearing potential are not eligible unless they commit to complete abstinence or have been on 2 methods of birth control, including 1 highly effective method and 1 additional method at the same time (unless committing to complete abstinence of heterosexual intercourse) at least 28 days (4 weeks) prior to study enrollment; sexually active females must also agree to remain on 2 methods of birth control, during treatment (including during dose interruptions), and continuing for at least 28 days after the completion of protocol therapy; examples of methods of contraception are as follows:
- •Highly effective methods (must use at least 1):
- •Intrauterine device (IUD)
- •Hormonal (prescription birth control pills, injections, implants)
- •Tubal ligation
- •Partner's vasectomy
- •Additional effective methods:
- •Male condom
- •Diaphragm
- •Cervical cap The two methods of birth control requirement applies to all sexually active females unless they have undergone a hysterectomy or bilateral oophorectomy
- •Female patients of childbearing potential (including those who commit to complete abstinence) are not eligible unless they agree to ongoing pregnancy testing and counseling every 28 days about pregnancy precautions and risks of fetal exposure
- •Male patients of child fathering potential are not eligible unless they have agreed to use latex condoms during intercourse with a woman of childbearing potential while receiving treatment and for 28 days thereafter
- •Patients with a history of thromboembolism unrelated to a central line, or patients with a known predisposition syndrome for thromboembolism are not eligible
- •Patients who have an uncontrolled or untreated infection are not eligible
- •Patients with known overt cardiac disease, including but not limited to a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia are not eligible
- •Patients with a significant systemic illness that is not well-controlled in the opinion of the treating physician are not eligible
研究组 & 干预措施
Arm I (low-dose lenalidomide)
Patients receive low-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Arm I (low-dose lenalidomide)
Patients receive low-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Arm II (high-dose lenalidomide)
Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Arm II (high-dose lenalidomide)
Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Number of Patients Who Demonstrate Complete or Partial Response
时间窗: 26 cycles of chemotherapy - up to 3 years after enrollment
Number of patients who demonstrate a complete or partial response as defined below: Complete Response - Complete disappearance of all known disease for at least 4 weeks; Partial Response - A reduction of at least 50% in the size of all measurable tumor as quantitated by the sum of the products of the largest diameters of measurable lesions when compared with that measurement at the time of study enrollment and maintained for at least 4 weeks.
Number of Patients Who Demonstrate Early Progression
时间窗: Up to 180 days after enrollment
Number of patients with disease progression during the first six months of protocol therapy. Disease progression is defined as ≥ 25% increase in the sum of the products of the largest diameters of the measurable lesions or the appearance of one or more new lesions when compared with the measurements of lesions at the time of enrollment.
次要结局
- Overall Survival [OS](Up to 3 years after study enrollment)
- Event-free Survival [EFS](Up to 3 years after study enrollment)
- Number of Patients With Toxic Events After 2 Dose Reductions(While receiving protocol therapy up to 3 years after study enrollment)
- Magnetic Resonance Imaging Sequence(Up to 3 years)
- Pharmacokinetic Parameters of Lenalidomide(Between days 5-21 of course 1 and each dose reduction)