A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological Clonal Non-Mast Cell Lineage Disease (AHNMD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
研究概览
简要总结
This pilot clinical trial studies brentuximab vedotin in treating patients with advanced systemic mastocytosis or mast cell leukemia. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them
详细描述
Brentuximab vedotin is an antibody with a covalently attached toxin. The antibody portion targets the protein CD30 on the surface of cells, and the toxin acts against those cells.
PRIMARY OBJECTIVES:
I. To evaluate the response rate to SGN-35 (brentuximab vedotin) in patients with tumor necrosis factor receptor superfamily, member 8 (CD30+) advanced systemic mastocytosis (SM) (ASM or mast cell leukemia [MCL] with or without an associated hematological clonal non-mast cell lineage disease [AHNMD]).
SECONDARY OBJECTIVES:
I. To evaluate the tolerability and safety profile of SGN-35 in patients with SM.
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
- •Written informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- •Life expectancy > 12 weeks
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN), if caused by ASM/MCL =< 5 x ULN
- •Serum direct bilirubin =< 1.5 x ULN; if considered related to ASM/MCL =< 3 x ULN
- •Serum creatinine =< 2.0 mg/dL
- •A diagnosis of systemic mastocytosis (SM) per 2008 World Health Organization (WHO) Criteria
- •Neoplastic mast cells must express CD30 by immunohistochemistry or flow cytometry
- •At least one of the eligible organ damage findings as defined by the international consensus response criteria
- •Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
- •Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test result within 7 days prior to the first dose of SGN-35
- •Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
排除标准
- •Unwilling or unable to comply with the protocol
- •Any other concurrent severe known disease (except carcinoma in-situ) or concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, or active uncontrolled infection) which could compromise participation in the study
- •History of another primary malignancy that has not been in remission for at least 3 years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou [PAP] smear)
- •Cardiovascular disease including congestive heart failure grade III or IV according to the New York Heart Association (NYHA) classification, left ventricular ejection fraction of < 50%, myocardial infarction within previous 6 months or poorly controlled hypertension
- •Pregnant or lactating
- •Neuropathy greater than or equal to grade 2
- •Known hypersensitivity to any excipient contained in the drug formulation
- •Confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
- •Presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (eg, AML)
- •Received any investigational agent, chemotherapy, interferon-alfa, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to Day 1
- •Received hematopoietic growth factor support within 14 days of Day 1 of SGN-35
- •Use of prednisone (or equivalent corticosteroid dose) for SM up to 10 mg/day or its equivalent is allowed, but it cannot have been started during screening; patients who are on prednisone up to 10 mg/day for medical problems unrelated to SM are also permitted on study
- •Presence of FIP1L1-PDGFR-alpha fusion even with resistance to imatinib
- •Received any treatment with SGN-35 prior to study entry
- •Any surgical procedure within 14 days of Day 1, excluding central venous catheter placement or other minor procedures (eg, skin biopsy)
研究组 & 干预措施
Brentuximab vedotin
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
干预措施: Brentuximab vedotin (Drug)
结局指标
主要结局
Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
时间窗: Up to 1 year
Overall response rate (ORR) is sum of complete response (CR); partial response (PR); and clinical improvement (CI) in 1 year, ie, ORR=CR+PR+CI. The outcome is the number of participants without dispersion. CR is following with response duration(RD) ≥12 weeks (wk) * No mast cell disease * Tryptase \<20 ng/mL * Neutrophils ≥1x10e9/L with normal differential * Hemoglobin ≥11 g/dL * Platelets ≥100x10e9/L * No hepatosplenomegaly * No systemic mastocytosis(SM)-related organ damage PR is following with RD ≥12wk * Neither CR or progressive disease(PD) * Neoplastic mast cells reduced ≥50% * Tryptase reduced ≥50% * 1+ disease finding resolved CI is following with RD ≥12wk * Neither CR; PR; or PD * 1+ of findings above Stable disease (SD) Not CR, PR, Cl, or PD Progressive disease (PD) Any of: * Worsening organ damage * Doubling of laboratory abnormality * New transfusion dependence of ≥4 units red cells or platelets at 8wk •+ ≥100% in transfusions for 8wk * 10-cm+ splenomegaly
次要结局
- Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score(Up to 1 year)
- Brentuximab Vedotin Toxicity(Up to 1 year)
- Percent Change of CD30 Expression on Neoplastic Mast Cells(Baseline and up to 1 year)
- Time to Response (TTR)(Up to 1 year)
- Progression-free Survival (PFS)(Up to 1 year)
- Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)(Up to 1 year)
- Duration of Response (DOR)(Up to 1 year)
研究者
Jason Robert Gotlib
Professor of Medicine (Hematology)
Stanford University