A Phase 2, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of AMD3100 (240 µg/kg) Added to a G-CSF Mobilization Regimen in Poor Mobilizing Adult Patients Who Have Previously Failed Stem Cell Collection/Attempts
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period
研究概览
简要总结
This study evaluates the safety, efficacy, and pharmacokinetics (PK) of plerixafor given in addition to granulocyte-colony stimulating factor (G-CSF) for collection of peripheral blood stem cells (PBSCs) for autologous transplantation in patients who would benefit from an autologous stem cell transplant but have failed previous collections or collection attempts with a mobilization regimen of G-CSF alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests.
The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of AMD3100 (plerixafor) on the evening prior to each day of apheresis.
Efficacy outcomes include quantification of CD34+ cells in the apheresis product and assessment of successful polymorphonuclear leukocyte (PMN) and platelet (PLT) engraftment after transplantation. PK outcomes include analysis of repeated doses of plerixafor.
详细描述
This is a Phase 2, multicenter, prospective, open-label study. Once 70 patients have enrolled, subsequent patients enrolled should have a diagnosis of lymphoma. Patients who would benefit from an autologous stem cell transplant, who have failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF) alone, chemotherapy and G-CSF, or any other conventional therapy including cytokines, chemotherapy and cytokines and bone marrow harvests, and who meet the inclusion/exclusion criteria are eligible to receive plerixafor as outlined in this protocol. The only change to standard of care of a mobilization regimen that includes G-CSF is the addition of a dose of plerixafor on the evening prior to each day of apheresis.
Patients will undergo mobilization with G-CSF (10 µg/kg) for 4 days. On Day 4, plerixafor (240 µg/kg) will be administered in the evening prior to the first apheresis and each subsequent evening prior to apheresis thereafter, such that there is a 10 to 11 hour interval between dosing and the initiation of apheresis. Patients will continue to receive G-CSF on each day of apheresis. Patients will undergo a minimum of 2 and a maximum of 7 aphereses or until ≥2*10^6 CD34+ cells/kg are collected, whichever occurs first. In addition, the mobilization of NHL tumor cells and the pharmacokinetics of repeat doses of plerixafor will be examined.
After the last apheresis has been completed, or after the patient has collected ≥2*10^6 CD34+ cells/kg, he/she will be treated with high-dose chemotherapy in preparation for transplantation. Patients will be transplanted with cells obtained from the G-CSF with plerixafor mobilization regimen. In the event that the minimum number of ≥2*10^6 cells for transplantation are not obtained from the first mobilization with plerixafor, cells may be retained and pooled for transplantation with those from a second mobilization with plerixafor (or from prior mobilization with other agents), at the investigator's discretion. If a second mobilization with plerixafor is attempted, a minimum rest interval of one week should be allowed between the last apheresis of the first regimen and the first dose of G-CSF of the second. The number of CD34+ cells mobilized in the peripheral blood (PB), collected in the apheresis product, and the number of apheresis sessions performed will be measured. Success of the transplantation will be evaluated by the time to engraftment of polymorphonuclear leukocytes (PMN) and platelets (PLT). Participants will be assessed for durability of their transplant for 12 months after transplantation.
This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.
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 78 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible to undergo autologous transplantation
- •Has failed previous collections or collection attempts with a mobilization regimen of granulocyte colony-stimulating factor (G-CSF), chemotherapy and G-CSF or any other conventional therapy including cytokines, chemotherapy and cytokines or bone marrow harvest.
- •Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
- •≥3 weeks since last cycle of chemotherapy (thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study) NOTE: Although thalidomide, dexamethasone, and Velcade™ are not considered prior chemotherapy for the purpose of this study, none are to be administered within 7 days prior to the first dose of G-CSF (see Exclusion Criteria).
- •The patient has recovered from all acute toxic effects of prior chemotherapy
- •White blood cell count (WBC) >2.5*10^9/L
- •Absolute neutrophil count >1.5*10^9/L
- •Platelet count >85*10^9/L
- •Serum creatinine ≤1.5 mg/dl
- •Creatinine clearance >60 ml/min
- •Aspartate aminotransferase (AST), alanine transaminase (ALT) and total bilirubin <2x upper limit of normal (ULN)
- •Left ventricle ejection fraction >45% (by normal echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan)
- •Forced expiratory volume in one minute (FEV1) >60% of predicted or diffusion lung capacity for carbon monoxide (DLCO) ≥45% of predicted
- •No active infection of hepatitis B or C
- •Negative for HIV
- •Signed informed consent
- •Women of child-bearing potential agree to use an approved form of contraception
排除标准
- •Once 70 patients have enrolled, patients with diagnoses other than lymphoma are not eligible (eg, acute myeloid leukemia, chronic lymphocytic leukemia, or multiple myeloma).
- •A co-morbid condition which, in the view of the investigators, renders the patient at high risk from treatment complications
- •A residual acute medical condition resulting from prior chemotherapy
- •Received Neupogen™, thalidomide, dexamethasone, and/or Velcade™ within 7 days prior to the first dose of G-CSF
- •Brain metastases or carcinomatous meningitis
- •Acute infection
- •Fever (temperature >38°C/100.4°F)
- •Hypercalcaemia (>1 mg/dL above the ULN)
- •Positive pregnancy test in female patients
- •Lactating females
- •Patients of child-bearing potential unwilling to implement adequate birth control
- •Patients whose actual body weight exceeds 175% of their ideal body weight
- •Patients who previously received experimental therapy within 4 weeks of enrolling in this protocol or who are currently enrolled in another experimental protocol during the Mobilization phase
研究组 & 干预措施
G-CSF plus Plerixafor
干预措施: G-CSF plus plerixafor (Drug)
结局指标
主要结局
Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment Period
时间窗: Day 1 to approximately day 38
Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for severity (mild, moderate, severe, life-threatening) and relatedness to study treatment (5 point scale from 'not related' to 'definitely related').
Proportion of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
时间窗: Day 5 to Day 11 (up to 7 apheresis)
Proportion of participants who reached the target of at least 2\*10\^6 CD34+ cells/kg collected during up to 7 aphereses.
Proportion of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Following Treatment With Plerixafor and G-CSF
时间窗: Day 5 to Day 11 (up to 7 aphereses)
Proportion of participants who reached the target of at least 5\*10\^6 CD34+ cells/kg collected during up to 7 apheresis.
次要结局
- Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment(approximately 2 months (1 month post transplant))
- Median Number of Days to Platelet (PLT) Engraftment(Approximately 2 months (1 month post transplant))
- Number of Participants With Durable Engraftment 12 Months After Autologous Transplantation(Approximately 13 months (12 months post transplant ))
- Number of Participants With Non-Hodgkin's Lymphoma (NHL) Who Had Evidence of Tumor Cell Mobilization After G-CSF or Plerixafor Administration(Up to Day 7)
- Number of Participants Who Achieved ≥2*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF(Day 5 up to Month 6 (up to 7 aphereses in each course of treatment))
- Number of Participants Who Achieved ≥5*10^6 CD34+ Cells/kg Collected During Both Courses of Treatment With Plerixafor and G-CSF(Day 5 up to Month 6 (up to 7 aphereses in each course of treatment))
- Maximum Observed Plasma Concentration (Cmax) on Day 4(Day 4 (following first plerixafor administration))
- Maximum Observed Plasma Concentration (Cmax) on Day 7(Day 7 (following fourth plerixafor administration))
- Time to Maximum Plasma Concentration (Tmax) on Day 4(Day 4 (following first plerixafor administration))
- Time to Maximum Plasma Concentration (Tmax) on Day 7(Day 7 (following fourth plerixafor administration))
- Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 4(Days 4 -5 (following first plerixafor administration))
- Area Under the Steady-state Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUC0-last) on Day 7(Days 7-8 (following fourth plerixafor administration))