NCT03386513进行中（未招募）1 期
A Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients With CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies
AbbVie32 个研究点 分布在 6 个国家目标入组 179 人开始时间: 2018年1月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 179
- 试验地点
- 32
- 主要终点
- Composite Complete Remission/Response (CCR) Rate As Assessed by Investigator in Frontline De Novo Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Participants
研究概览
简要总结
This is an open-label, multi-center, Phase 1/2 study to determine the MTD and assess the safety, tolerability, PK, immunogenicity, and anti-leukemia activity of IMGN632 when administered as monotherapy to patients with CD123+ disease.
详细描述
IMGN632 is administered by IV on Day 1 of each cycle, with cycles repeating every 21 days.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease Characteristics:
- •a. Confirmation of CD123 positivity by flow cytometry or IHC. Participants who received prior CD123-targeting agents will be allowed as long as the blasts still have detectable CD123 expression.
- •Expansion inclusion:
- •Cohort 1 - Participants with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) with 1-3 prior lines of therapy
- •Cohort 2 - Participants with relapsed AML
- •Cohort 3 - Participants with relapsed relapsed or refractory ALL (including any subtypes: B-cell, T-cell, Ph+ and Ph-)
- •Cohort 4 - Participants with relapsed or refractory other hematologic malignancies not included in the cohorts above (eg, high risk/very high-risk MDS, MPN, CMML, BP-CML).
- •Cohort 5 - Participants with relapsed relapsed or refractory (to nonintense therapies) CD123+ AML.
- •Cohort 6 - Participants with frontline de novo BPDCN at screening who have not received prior systemic therapy and participants with frontline BPDCN who have PCHM and have not received prior systemic therapy.
- •Note: Participants in Cohort 6 may have received local therapy (radiotherapy, surgical excision, photodynamic therapy). Eligible participants must have a recurrence or progression in the field of local therapy OR disease outside the field of local therapy.
排除标准
- •Participants who, in the judgment of their treating physician, have appropriate standard of care therapies will be excluded from Cohorts 1 through
- •Frontline BPDCN participants with central nervous system (CNS) disease will be excluded. A lumbar puncture must be performed during the 28-day screening period, prior to drug administration. Relapsed or refractory BPDCN participants with a known history of CNS disease must have been treated locally, have at least 1 lumbar puncture with no evidence of CNS disease, and must be clinically stable prior to first dose. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted with the approval of the Sponsor.
- •Participants with a history of veno-occlusive disease (sinusoidal obstruction syndrome) of the liver.
- •Participants with a history of Grade 4 capillary leak syndrome, or non-cardiac Grade 4 edema are ineligible, eg, related to tagraxofusp-erzs or other etiology.
- •Interval from prior cancer therapy:
- •For frontline BPDCN participants with prior local therapy (eg, radiotherapy), participants must not have received treatment within 14 days prior to drug administration on this study.
- •Relapsed or refractory BPDCN participants must not have received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agents within 14 days prior to drug administration on this study. Participants must have recovered to baseline from all acute toxicity from this prior therapy.
- •Note: the exception that participants who have received a checkpoint inhibitor must not have received that therapy within 28 days prior to drug administration on this study.
研究组 & 干预措施
Escalation and Expansion
Experimental
Escalation: IMGN632 was administered by IV on 2 different schedules for participants with relapsed/refractory AML, ALL, or BPDCN.
Expansion: IMGN632 was administered by IV:
- Cohort 1: Relapsed or refractory BPDCN participants who have received 1-3 prior systemic therapies (incl. tagraxofusp-erzs and/or any other systemic therapy deemed appropriate for the treatment of BPDCN)
- Cohort 2: Relapsed AML
- Cohort 3: Relapsed or refractory ALL
- Cohort 4: Other relapsed or refractory hematologic malignancies
- Cohort 5: Relapsed or refractory AML at alternate dose or schedule
- Cohort 6: Pivotal cohort for frontline BPDCN participants who have not received prior systemic therapy and participants with frontline BPDCN who have prior or concomitant hematologic malignancy (PCHM) and have not received prior systemic therapy.
干预措施: IMGN632 (Drug)
结局指标
主要结局
Composite Complete Remission/Response (CCR) Rate As Assessed by Investigator in Frontline De Novo Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Participants
时间窗: Up to approximately 81 months
CCR rate was defined as percentage of participants with complete remission/response (CR) and clinical complete remission (CRc). CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/microliter \[μL\]) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on computed tomography (CT); and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
Escalation Phase: MTD and RP2D
Escalation Phase: MTD and RP2D
BPDCN: CR+clinical CR [CRc]
BPDCN: CR+clinical CR [CRc]
次要结局
- Dose Escalation Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to approximately 81 months)
- Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs)(Up to approximately 81 months)
- Maximum Plasma Concentration (Cmax) of IMGN632 (Antibody Drug Conjugate [ADC]) and Total Antibody(Cycle 1 and Cycle 3 (each cycle length = 21 days))
- Cmax of FGN849(Cycle 1 and Cycle 3 (each cycle length = 21 days))
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IMGN632 (ADC) and Total Antibody(Cycle 1 and Cycle 3 (each cycle length = 21 days))
- AUC0-last of FGN849(Cycle 1 and Cycle 3 (each cycle length = 21 days))
- Number of Participants With Anti-drug Antibodies (ADAs) at Any Post-baseline Visit(Up to approximately 81 months)
- Dose Escalation Phase: Overall Response Rate (ORR), As Assessed by Investigator in Participants With AML(Up to approximately 81 months)
- Dose Escalation Phase: CR+CRh Rate, As Assessed by Investigator in Participants With AML(Up to approximately 81 months)
- Dose Escalation Phase: CR+CRh+CRi Rate, As Assessed by Investigator in Participants With AML(Up to approximately 81 months)
- CCR Rate As Assessed by Investigator in Participants With Relapsed/Refractory (R/R) BPDCN(Up to approximately 81 months)
- Duration of CCR (DOCR) As Assessed by Investigator in Frontline De Novo BPDCN Participants With CR or CRc(Up to approximately 81 months)
- DOCR As Assessed by Investigator in R/R BPDCN Participants With CR or CRc(Up to approximately 81 months)
- DOCR As Assessed by Investigator in Total Frontline BPDCN Participants With CR or CRc(Up to approximately 81 months)
- Number of Participants With TEAEs in Participants Who Received IMGN632 As a Single Agent at the RP2D Level (0.045 mg/kg)(Up to approximately 81 months)
- Rate of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants(Up to approximately 81 months)
- Duration of CR+CRc+CRh As Assessed by Investigator in Total R/R BPDCN Participants(Up to approximately 81 months)
- ORR As Assessed by Investigator in Total R/R BPDCN Participants(Up to approximately 81 months)
- Duration of Overall Response As Assessed by Investigator in Total R/R BPDCN Participants(Up to approximately 81 months)
- Overall Survival in Total R/R BPDCN Participants(Up to approximately 81 months)
- CCR Rate As Assessed by Investigator in All Frontline BPDCN Participants With Post-Treatment Consolidative Stem Cell Transplant (SCT)(Up to approximately 81 months)
- CCR Rate As Assessed by Investigator in All R/R BPDCN Participants With Post-Treatment Consolidative SCT(Up to approximately 81 months)
- Percentage of Participants With Post-baseline Transfusion Independence in BPDCN Participants(Up to approximately 81 months)
- Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and DLTs
- PK parameters, including but not limited to observed maximum concentration (Cmax) and area under the concentration versus time curve (AUC)
- To evaluate the potential immunogenecity of IMGN632 - ADA
- Overall response rate (OOR) (CR without minimal residual disease [CRMRD- ] + CR + complete remission with partial hematologic recovery [CRh] + complete remission with incomplete recovery [CRi] + morphologic leukemia-free state [MLFS] + partial response [PR]), complete remission rate (CRMRD-, CR, CRh), composite complete remission (CCR) rate (CRMRD-, CR, CRh, CRi), and time to event outcomes (duration of overall response [DOR], event-free survival, relapse-free survival, OS).
- BPDCN Expansion Phase (Cohorts 1 and 6): CR+CRc
- BPDCN Expansion Phase (Cohorts 1 and 6): ADA
- BPDCN Expansion Phase (Cohorts 1 and 6): Conversion rate to independence of red blood cell and platelet transfusion relative to baseline
研究者
研究点 (32)
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