Potential of Immunotherapy to Convert a Complete Cytogenetic Remission in Chronic Myelogenous Leukemia to a Molecular Complete Remission: Randomized Phase II Study of Proteinase 3 PR1 Peptide Mixed With Montanide ISA-51 VG Adjuvant and Administered With GM-CSF and Peginterferon Alfa-2b [PEG-INTRON(R), Schering Corporation]
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Molecular Response Rate
研究概览
简要总结
The goal of this clinical research study is to find out if using the PR1 peptide vaccine (PR1) without PEG-Intron® (interferon) or in combination with interferon can reduce or eliminate disease in patients who have CML that is in cytogenetic remission after treatment with imatinib mesylate, but who still have small amounts of disease able to be noticed (detected). Researchers want to see if giving low doses of interferon together with PR1 may make the vaccine more effective. The safety of treatment in this study will also be studied.
详细描述
Your disease responded well to treatment with imatinib mesylate. It is in complete cytogenetic remission. This means that the Philadelphia chromosome (Ph), a change in genetic material that is believed to lead to leukemia, is no longer detectable (by the standard chromosome analysis) in your bone marrow and blood cells. A molecular remission, which is what researchers want you to achieve, means a greater reduction or a complete elimination of the Ph.
The small amounts of disease can be detected using a technique called polymerase chain reaction (PCR). This is a very powerful test that can detect very small amounts of disease that can still be present in the bone marrow and/or blood cells.
PR1 is an experimental vaccine made from a protein that is found in large amounts in leukemia cells in CML.
Imatinib mesylate (which you are already receiving as standard therapy) is designed to bind to certain proteins on the tumor cells, which may prevent the cells from growing.
Interferon is a drug that was used as standard therapy for patients with CML before imatinib mesylate was available. It can help the immune system to function more effectively (causing leukemia cells to show more PR1), which may make leukemia cells a better target to be killed.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Patients >/= 18 years with Philadelphia chromosome (Ph)- or BCR/ABLpositive CML (as determined by cytogenetics, FISH, or PCR).
- •Patients must have received imatinib therapy for at least 18 months and not have increased their dose of imatinib in the last 6 months.
- •Patients must be in complete cytogenetic remission.
- •Patients must have detectable BCR-ABL transcript levels meeting at least one of the following criteria: 1) Patient has never achieved a major molecular response (i.e., never reached levels <0.05%), and transcript levels have shown in at least two consecutive measures separated by at least 1 month to have increased by any value, or
- •continued from above: 2) Achieved a major molecular response that has been lost with an increase in transcript levels by at least 1-log over two consecutive analyses separated by at least 1 month, or 3) BCR-ABL transcript levels have reached a plateau defined as a ratio that is not more than 0.25-log (one fourth of a log) lower than the lowest value obtained in the last at least 6 months, with at least 2 values obtained during this period.
- •Patients must not have had a continuous interruption of imatinib therapy of greater than 14 days or any interruptions totaling 6 weeks within the 6 months prior to enrollment.
- •Patients must be HLA-A2 positive at one allele
- •Patients must give informed consent and sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
- •Eastern Cooperative Oncology Group (ECOG) performance status </=
- •Adequate organ function defined as: bilirubin <2 times upper limit of normal (ULN), creatinine <1.5 times ULN, and serum glutamate pyruvate transaminase (sGPT) <2.5 times ULN.
- •Women of childbearing potential should practice effective methods of contraception.
排除标准
- •Patients with a history or clinical evidence of autoimmune disorders
- •Patients receiving immunosuppressive therapy including cyclosporine, or FK506 within 3 months of study entry
- •Chronic use (> 2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 28 days of the first day of study drug treatment (topical and inhaled corticosteroids are permitted)
- •GM-CSF or interferon administration within 1 month of first PR1 injection
- •Patients receiving any other investigational agents currently or within the past 4 weeks. Patients must have recovered from any adverse effects of investigational therapy.
- •Patients who are pregnant or breast-feeding
- •Patients with clinically significant heart disease (New York Heart Association (NYHA) Class III or IV)
- •Patients with positive cANCA
- •History of HIV positivity or AIDS
- •Chloroma at time of study screening
- •Prior vaccine therapy for Chronic myelogenous leukemia (CML)
- •Known allergy to Montanide ISA-51 VG adjuvant
研究组 & 干预措施
PR1 + Imatinib
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Continue receiving imatinib by mouth at the same dose received during the last 6 months. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: Peptide Vaccine (PR1 Peptide) (Biological)
PR1 + Imatinib
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Continue receiving imatinib by mouth at the same dose received during the last 6 months. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: Imatinib (Drug)
PR1 + Imatinib
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Continue receiving imatinib by mouth at the same dose received during the last 6 months. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: GM-CSF (Drug)
PR1 + Imatinib + Interferon
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: Peptide Vaccine (PR1 Peptide) (Biological)
PR1 + Imatinib + Interferon
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: Peginterferon alfa-2b (Drug)
PR1 + Imatinib + Interferon
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: Imatinib (Drug)
PR1 + Imatinib + Interferon
PR1 peptide will be administered at a dose of 0.5 mg of PR1 on weeks 0, 3, 6 and 18 for a total of 4 doses. Subcutaneous injection of interferon 0.5 microg/kg with each PR1 vaccination. GM-CSF 75 micrograms subcutaneously in the same area as the vaccine with every vaccination.
干预措施: GM-CSF (Drug)
结局指标
主要结局
Molecular Response Rate
时间窗: Baseline to 18 weeks, up to 6 months post final vaccination for overall study participation period.
Molecular response rate is number of respondents compared to total participants. Molecular Response is defined as a greater than a one-log reduction of Breakpoint Cluster Region-Abelson Murine Leukemia (BCR-ABL) transcript levels by quantitative polymerase chain reaction (PCR) from the baseline level at the time vaccination was initiated, or a disappearance of BCR-ABL transcripts, as measured by reverse transcription polymerase chain reaction (RT-PCR), occurring within 6 months from the last vaccination. Participants receive a series of 4 vaccinations administered at 3-week intervals and the fourth (final) vaccination administered 3 months after the third vaccination with blood draw to test PCR following every 3 months to test the level of leukemia in the blood and to see if disease is responding to the vaccine.
次要结局
- Number of Participants With Immunologic Response(Period of 18 weeks (i.e., one vaccination each on weeks 0, 3, 6, and 18).)