Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 23
- 主要终点
- Number of Patients With Severe Toxicities
研究概览
简要总结
The purpose of this study is to evaluate the clinical activity and safety of a WT1 Antigen-Specific Cancer Immunotherapeutic (WT1 ASCI) as post-induction therapy in adult patients with WT1-positive AML presenting a suboptimal clinical response to induction chemotherapy. The study will also assess whether this treatment induces a specific immune response to the malignancy.
详细描述
At least 40 patients will be enrolled in this study, divided in two cohorts of 20 patients each. One cohort will include patients in partial remission after induction therapy and one cohort will include patients in complete remission but with incomplete blood count recovery. Patients in both cohorts will receive the same study treatment according to the same administration schedule.
This protocol summary has been updated according to the Protocol Amendment 3 (dated 10 Sept 2014).
All active follow-up visits and procedures after the concluding visit, 30 days after the last treatment administration, will be stopped In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.Blood sampling for safety monitoring as per protocol will continue.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •The patient has cytologically proven AML as defined by the World Health Organization (WHO) classification. The pretreatment AML karyotype should be documented.
- •The leukemia is a de novo or secondary AML.
- •The patient's blasts cells show expression of WT1 transcript, detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR).The patient received the following therapy according to the Institution's standard of care.
- •For patients < 60 years old: at least two induction chemotherapy treatments.
- •For patients >= 60 years old: at least one induction chemotherapy treatment or alternative treatment.
- •The first ASCI administration should be given within one year after the last chemotherapy administration. All screening procedures should be completed within seven weeks before the first ASCI administration.
- •In the investigator's opinion and in compliance with the Institution Hematology Tumor Board's guidances, the patient should not be eligible for any additional chemotherapy treatment before the ASCI treatment.
- •The clinical status of the patient at inclusion is one of the following:
- •Partial Remission (PR)
- •Morphologic complete remission with incomplete blood count recovery (CRi)
- •Written informed consent has been obtained prior to the performance of any protocol-specific procedure.
- •The patient is >= 18 years of age at the time of signature of the first informed consent form.
- •Eastern Cooperative Oncology Group performance status of 0, 1 or
- •Adequate hepatic and renal function defined as:
- •Serum bilirubin < 1.5 times the Upper Limit of Nor-mal (ULN).
- •Serum ALT < 2.5 times the ULN.
- •Calculated creatinine clearance > 50 mL/min.
- •In the view of the investigator, the patient can and will comply with the requirements of the protocol.
- •If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, then she must practice adequate contraception for 30 days prior to treatment administration, have a negative pregnancy test and continue such precautions for 2 months after completion of the treatment administration series.
排除标准
- •The patient was diagnosed with leukemic Central Nervous System (CNS) disease (e.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement.
- •The patient has acute promyelocytic leukemia with t(15;17) (q22;q12), (PML/RARα) or variants.
- •The patient has received, or is receiving, allogeneic Stem Cell Transplantation (SCT).
- •The patient has received Fludarabine, Clofarabine or Cloretazine within 12 months preceding the ASCI treat-ment.
- •The patient has hypercalcemia.
- •The patient is known to be HIV-positive.
- •The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and in-flammatory bowel disease. Patients with vitiligo are not excluded.
- •The patient has a history of allergic reactions likely to be exacerbated by any component of the study investigational product.
- •The patient has other concurrent severe medical prob-lems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
- •The patient has another metastatic cancer disease.
- •The patient has a history of congestive heart failure, coronary artery disease or previous myocardial infarction.
- •The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
- •The patient has received any investigational or non-registered medicinal product other than the study treat-ment within 30 days preceding the first dose of study treatment or plans to receive such a drug during the study period.
- •The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
- •The patient is receiving full dose subcutaneous heparins or is under anti-coagulation treatment.
- •For female patients: the patient is pregnant or lactating.
研究组 & 干预措施
Partial Remission Group
Adult patients in partial remission post-induction chemotherapy, who received the GSK2130579A study product, administered sequentially, as follows: Cycle 1: 6 doses, each given at 2-week intervals; Cycle 2: 6 doses, each given at 3-week intervals; Cycle 3: 4 doses, each given at 6-week intervals; Cycle 4: 4 doses, each given at 3-month intervals, followed by 4 doses each given at 6-month intervals.
干预措施: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A (Biological)
Complete Remission Group
Adult patients in complete remission with incomplete blood count recovery post-induction chemotherapy, who received the GSK2130579A study product, administered sequentially, as follows: Cycle 1: 6 doses, each given at 2-week intervals; Cycle 2: 6 doses, each given at 3-week intervals; Cycle 3: 4 doses, each given at 6-week intervals; Cycle 4: 4 doses, each given at 3-month intervals, followed by 4 doses each given at 6-month intervals.
干预措施: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A (Biological)
结局指标
主要结局
Number of Patients With Severe Toxicities
时间窗: During the entire study (from Month 0 to Month 49)
Severe toxicities (as classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0) during the study treatment period defined as a study product-related or possibly study product-related: * Grade 4 toxicity (exception: study product-related or possibly study product-related Grade 4 fatigue - including lethargy, asthenia, and malaise - had to have a duration of at least 48 hours to be taken into account). * Grade 3 toxicity lasting for at least 48 hours (exceptions: myalgia, arthralgia, headache, and fever, regardless of duration). * Grade 2 toxicity (i.e., rash, flushing, urticaria, and dyspnea). Drug fever was not part of this definition. * Decrease in renal function, with a calculated creatinine clearance \< 40 mL/min. * Grade 2 cardiac ischemia/infarction (i.e., asymptomatic and testing suggesting ischemia; stable angina).
Number of Patients With Best Overall Response, Defined by Either Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD)
时间窗: During the entire study (from Month 0 to Month 49)
CR = having \< 5% blasts in aspirate sample with marrow spicules and with a count of ≥ 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease; different phenotype (by flow cytometry) to the pre-treatment specimen; absolute neutrophil count \> 1000/mm3; platelet count ≥ 100 000/mm3 and being independent of red blood cell (RBC) transfusions. PR = a decrease of ≤ 50% in the % of blasts in bone marrow aspirate compared to Visit 4; being independent of RBC transfusions and the absolute neutrophil ≥ 1000/mm3 and platelet counts and ≥ 100 000/mm3. SD = no sufficient criteria for CR, a PR or Progressive disease (PD = Reappearance of leukemic blasts in the peripheral blood; Reappearance/development of cytologically proven extramedullary disease, Appearance of new dysplastic changes, or in a bone marrow aspirate sample (with marrow spicules and with a count of ≥200 nucleated cells) of ≥5% blasts; or, in case of early progression, a higher blast % than at Visit 4).
次要结局
- Anti-WT1 Seropositivity Rate(At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4)
- Anti-WT1 Antibody Concentrations(At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4)
- Anti-WT1 Antibody Response(At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4)
- Number of Subjects With Any and Related Unsolicited Adverse Events (AEs)(Starting with the first administration of study treatment and ending 30 days after the last study treatment administration)
- Number of Subjects With Study Treatment Failure(During the entire study (from Month 0 to Month 49))
- Number of Subjects With Any or Related Serious Adverse Events (SAEs)(During the entire study (from Month 0 to Month 49))
- Number of Patients With Abnormal Hematological and Biochemical Parameters(During the entire study (Month 0 to Month 49))