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Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia

2017年3月2日 更新者：Pfizer

An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia

The Phase 1 portion of this study will assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule. The Phase 2 portion of the study will evaluate the efficacy of inotuzumab ozogamicin as measured by hematologic remission rate (CR + CRi) in patients in second or later salvage status.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

72

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • California
      • Duarte、California、美国、91010-3000
        • City of Hope National Medical Center
      • Palo Alto、California、美国、94304
        • Stanford Unversity Cancer Clinical Trials Office
      • Palo Alto、California、美国、94304
        • Stanford Unversity Hospital and Clinics, CTRU
      • Stanford、California、美国、94305
        • Stanford Cancer Institute
      • Stanford、California、美国、94305
        • Stanford University Hospital and Clinics
    • Illinois
      • Chicago、Illinois、美国、60637
        • The University of Chicago Medical Center
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Beth Israel Deaconess Medical Center
      • Boston、Massachusetts、美国、02215
        • Dana-Farber Cancer Institute
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital (MGH)
      • Boston、Massachusetts、美国、02115
        • Brigham and Women's Hospital (BWH)
    • Michigan
      • Detroit、Michigan、美国、48201
        • Karmanos Cancer Institute
      • Farmington Hills、Michigan、美国、48334
        • Karmanos Cancer Institute at Farmington Hills
    • Ohio
      • Cleveland、Ohio、美国、44195
        • Cleveland Clinic
    • Texas
      • Houston、Texas、美国、77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle、Washington、美国、98109
        • Seattle Cancer Care Alliance

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). Subjects enrolled in the Phase 2 portion of the study must be due to receive salvage 2 or later therapy.
  • Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
  • Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

  • Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia.
  • Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry.
  • Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Inotuzumab Ozogamicin
药品：Inotuzumab Ozogamicin

Part 1: Administered intravenously as 2 - 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total dose per cycle 0.8 mg/m^2 to 2.0 mg/m^2.

Part 2 Expansion and Part 3 Phase 2: Administered intravenously as 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total initial dose per cycle 1.8 mg/m^2.

其他名称：
  • CMC-544

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase
大体时间：Cycle 1
DLT was any of the following in the first cycle & attributable to inotuzumab ozogamicin: any greater than or equal to (≥) Grade 4 non-hematologic toxicity except nausea/vomiting (if manageable with supportive care), alopecia, & toxicities secondary to neutropenia & sepsis; prolonged myelosuppression (absolute neutrophil count [ANC] less than [<] 500 per microliter [/µL] or platelet count <25,000/µL in bone marrow with <5 percent (%) blasts & no evidence of leukemia more than 45 days beyond the most recent dose of test article); any Grade 3 non-hematologic toxicity (excluding toxicities such as alopecia or those secondary to neutropenia & sepsis) not resolving to ≥ Grade 2 within 7 days of the most recent dose of test article or was clinically significant irrespective of duration; any ≥ Grade 3 elevation of alanine aminotransferase, aspartate aminotransferase or bilirubin lasting ≥7 days; any test article related toxicity resulting in permanent discontinuation of test article.
Cycle 1
Percentage of Participants With Preliminary Satisfactory Response (Complete Response [CR], CR With Incomplete Count Recovery [CRi], Partial Response [PR], or Resistant Disease [RD]) Indicating Disease Stability After First Dose During Phase 1 Dose-Finding
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was the disappearance of leukemia indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was as for CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was an improved or no worsening of acute lymphocytic leukemia indicated by no peripheral blood blasts, and/or at least a 50% decrease in the marrow blast percentage, compared to pre-treatment value, and marrow blast percentage ≥5% and less than or equal to (≤)25% and/or C2 extramedullary disease status. RD occurred if a participant survived ≥7 days following completion of initial treatment course and had persistent leukemia in the most recent peripheral blood smear or bone marrow and/or persistent disease involvement at any extramedullary site after completion of therapy.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR or CRi During Phase 2
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR, CRi or PR During the Phase 1 Expansion Phase
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
From screening to progressive disease or another induction therapy started, up to approximately 2 years

次要结果测量

结果测量
措施说明
大体时间
Percentage of Participants With CR, CRi or PR in Phase 2
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Number of Participants With Minimal Residual Disease (MRD) Negativity in Participants Achieving CR and CRi
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
MRD negativity was defined as <0.01% mononuclear cells.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR or CRi by Cytogenetic Category
大体时间：From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants Who Had a Post-Treatment Stem-Cell Transplant (SCT)
大体时间：Up to approximately 2 years from first dose
Post-treatment SCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin.
Up to approximately 2 years from first dose
Progression Free Survival (PFS)
大体时间：Up to approximately 2 years from first dose
PFS was defined as the time from Cycle 1 Day 1 to first documentation of PFS event (earliest date of objective progression [PD], treatment discontinuation due to global deterioration of health status, subsequent induction or transplant after best response of PR or resistant disease, relapse after CR or CRi, or death due to any cause). Participants last known to be 1) alive and 2) without a PFS event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Duration of Remission (DoR1) for Participants Who Achieved CR or CRi
大体时间：Up to approximately 2 years from first dose
DoR1 was defined for participants who responded as the time from the date of first documentation of Complete Hematologic Response (CR or CRi) to the date of the first documentation of relapse after CR or CRi, treatment discontinuation due to global deterioration of health status) or to death due to any cause. Participants last known to be 1) alive and 2) without a DoR1 event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Duration of Response (DoR) for Participants Who Achieved CR/CRi or PR
大体时间：Up to approximately 2 years from first dose
DoR was defined for participants who respond as the time from the date of first documentation of Hematologic Response (CR, CRi, or PR) to the date of the first documentation of DoR event (earliest date of PD, treatment discontinuation due to global deterioration of health status, first induction therapy or transplant after PR, relapse after CR or CRi or death due to any cause). Participants last known to be 1) alive and 2) without a DoR event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Overall Survival (OS)
大体时间：Up to approximately 2 years from first dose
OS was defined as the time from Cycle 1 Day 1 to date of death due to any cause. If death was not documented, censoring occurred at the date at which the participant was last known to be alive.
Up to approximately 2 years from first dose
Time to Remission for Participants Who Achieved CR or CRi
大体时间：Up to approximately 2 years from first dose
Time to remission was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic remission (CR or CRi) in participants achieving remission during study therapy.
Up to approximately 2 years from first dose
Time to Response for Participants Who Achieved CR/CRi or PR
大体时间：Up to approximately 2 years from first dose
Time to response was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic response (CR, CRi, or PR).
Up to approximately 2 years from first dose
Time to MRD Negativity for Participants Who Achieved CR or CRi
大体时间：Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
Time to MRD negativity was defined as the time from the date of first dose of study drug to the date of first documentation of MRD negativity.
Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
Duration of Follow-Up
大体时间：From first dose up to approximately 2 years
Duration of follow-up was defined as the time from the date of first dose of study drug to the date of last contact for participants known to be alive.
From first dose up to approximately 2 years
Percentage of Cluster of Differentiation-22 Positive (CD22+) Leukemic Blasts in Abnormal B Cells in Blood by Visit
大体时间：Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
CD22+ leukemic blasts assessed in abnormal B cells from blood (data from central laboratories only).
Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
Percentage of CD22+ Leukemic Blasts in Abnormal B Cells in Bone Marrow by Visit
大体时间：Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
CD22+ leukemic blasts assessed in abnormal B cells from bone marrow (data from central laboratories only).
Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
Messenger Ribonucleic Acid (mRNA) Gene Expression
大体时间：Predose and postdose on Days 1 and 15 of Cycle 1
Optional blood samples for pharmacogenomic parameters were collected during Cycle 1 prior to the start of the inotuzumab ozogamicin infusion (0 hours) and 1 hour post-dose (original Final Protocol and Protocol Amendments 1 and 2) or 3 hours post-dose (Protocol Amendments 3 and 4) on Day 1 and Day 15 from those participants who provided consent. Gene expression analysis of samples collected pre- and post-dosing was performed using 96-gene TaqMan® low density array cards to examine the concordance between clinical outcome and expression of genes such as those involved in DNA damage response, apoptosis, B-cell antigen expression, glutathione metabolism, drug transport and the phosphoinositide 3-kinase/mammalian target of rapamycin pathway. Expression for each gene was reported as a normalized value, 2^-change in (∆) threshold cycle (Ct), where ∆Ct is Ct^target gene minus Ct^reference genes, averaged.
Predose and postdose on Days 1 and 15 of Cycle 1

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Pfizer

合作者

UCB Pharma

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2011年8月1日

初级完成 (实际的)

2014年8月1日

研究完成 (实际的)

2016年1月1日

研究注册日期

首次提交

2011年5月11日

首先提交符合 QC 标准的

2011年5月27日

首次发布 (估计)

2011年6月1日

研究记录更新

最后更新发布 (实际的)

2017年4月13日

上次提交的符合 QC 标准的更新

2017年3月2日

最后验证

2017年3月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • B1931010
  • 3129K6-1106 (其他标识符：Alias Study Number)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

急性淋巴细胞白血病的临床试验

  • Shenzhen Second People's Hospital
    招聘中
    中国 CML 患者停用 TKI (TFR_china)
    白血病 | 骨髓的 | 慢性的 | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | 积极的
    中国

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