Phase I Study of Carfilzomib-based Chemotherapy Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This phase I study utilizes a 3+3 design with escalating cohorts of Carfilzomib at 20mg/m2, 27mg/m2, 36mg/m2, 45mg/m2, 56mg/m2, and 70mg/m2 to be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone and Granulocyte colony-stimulating factor (G-CSF)
详细描述
This study will be conducted as an open-label Phase I, single-center study in which subjects will receive carfilzomib, in combination cyclophosphamide and dexamethasone, for mobilization of peripheral blood stem cells. Study treatment will be administered in sequential cohorts, with three to six subjects in each cohort.
Following induction therapy, eligible patients will complete screening procedures. Treatment will consist of Dexamethasone 40mg IV/PO to be administered as a premedication. Carfilzomib dosed at each respective cohort level to be administered over 30 minutes followed by Cyclophosphamide dosed at 2gm/m2 administered over 1 hour.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
On day 7 subjects will initiate high dose G-CSF injections at 14mcg/kg daily (with a cap of 1440mcg daily). On day 12 peripheral blood stem cell collection will begin per institutional protocol.
After successful peripheral blood stem cell mobilization, patients will proceed to a melphalan based autologous stem cell transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Subject has voluntarily agreed to participate by giving written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Informed Consent must be obtained prior to mobilization.
- •Subject has a confirmed diagnosis of multiple myeloma as specified by the International Myeloma Working Group criteria and must have measurable disease as defined by at least one of the following criteria:
- •Serum monoclonal protein ≥ 0.5 g/dL
- •≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
- •Serum immunoglobulin free light chain: involved FLC ≥ 10 mg/dL (≥ 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- •MRD positivity in peripheral blood by flow cytometry.
- •Subject previously received treatment with Carfilzomib.
- •Subject is ≥18 years of age at the time of signing the informed consent form.
- •Subject has an ECOG performance status of <
- •Subjects must have completed any "induction therapy" and have achieved less than a CR.
- •Subject has a life expectancy of >12 weeks.
- •Absolute neutrophil count (ANC) ≥1000 cells/mm3 (≥500 for patients with bone marrow biopsy displaying >50% involvement by myeloma)
- •Platelets count ≥ 50,000/mm3 (≥ 30,000 for patients with bone marrow biopsy displaying >50% involvement by myeloma)
- •Hemoglobin > 9.0 g/dL
- •Serum SGOT/AST <3.0 x upper limits of normal (ULN)
- •Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
- •Serum total bilirubin <1.5 x ULN
- •Subject must have a MUGA scan or echo with LVEF ≥40% within 6 months of enrollment.
- •Females of childbearing potential (FCBP) must have a negative serum pregnancy test should be done within 7 days of treatment initiation and a negative urine pregnancy test within the 24 hours prior to the first study drug administration
- •FCBP and male subjects who are sexually active with FCBP must agree to use 2 highly effective concomitant methods of contraception including a male condom during the study and for 90 days following the last dose of study treatment
- •Male subjects must agree to not donate sperm while taking carfilzomib and for 90 days after the last dose of carfilzomib.
排除标准
- •Subject has a history of allergic reactions to compounds containing captisol, or Carfilzomib
- •Subject has a NYHA Class III or IV heart disease and/or a history of active unstable angina, congestive heart disease, severe uncontrolled cardiac arrhythmia, electrocardiographic evidence of acute ischemia, active conduction system abnormalities or myocardial infarction within 6 months prior to enrollment. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- •Uncontrolled hypertension.
- •Pulmonary hypertension.
- •Known HIV infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study).
- •Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
- •Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).
- •Subject has ≥Grade 2 peripheral neuropathy.
- •Subject has been diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- •Subject has received radiation therapy within 3 weeks of enrollment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
- •Subject has had prior mobilization or stem cell transplant.
研究组 & 干预措施
Carfilzomib Mobilization - Dose Level 0
Carfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 0
Carfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
Carfilzomib Mobilization - Dose Level 2
Carfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 2
Carfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 3
Carfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 4
Carfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 4
Carfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 0
Carfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 1
Carfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 2
Carfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 3
Carfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
Carfilzomib Mobilization - Dose Level 3
Carfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 4
Carfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 5
Carfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Carfilzomib Mobilization - Dose Level 0
Carfilzomib at 20mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 1
Carfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 1
Carfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 1
Carfilzomib at 27mg/m2 over 10 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
Carfilzomib Mobilization - Dose Level 2
Carfilzomib at 36mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
Carfilzomib Mobilization - Dose Level 3
Carfilzomib at 45mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 4
Carfilzomib at 56mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
Carfilzomib Mobilization - Dose Level 5
Carfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Cyclophosphamide (Drug)
Carfilzomib Mobilization - Dose Level 5
Carfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Carfilzomib (Drug)
Carfilzomib Mobilization - Dose Level 5
Carfilzomib at 70mg/m2 over 30 minutes will be administered concomitantly with Cyclophosphamide 2 gm/m2, Dexamethasone 40mg and G-CSF.
For patients who are naïve to carfilzomib based therapy a priming dose of Carfilzomib (20mg/m2) will be administered 1 week prior to the cohort dosing.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: 28 Days
To determine the maximum tolerated dose (MTD) of carfilzomib in combination with cyclophosphamide, dexamethasone and G-CSF in mobilizing and collecting peripheral blood stem cells
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 24 Months
Safety and tolerability will be assessed by clinical review of all relevant parameters including Adverse Events (CTCAE v4.0)
次要结局
未报告次要终点