A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigators Choice of Best Available Therapy in Subjects with Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second-Line Salvage Therapy
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 116
- 试验地点
- 5
- 主要终点
- The primary objective of the trial is to compare the efficacy of GPS to Investigators choice of BAT on OS in subjects with AML who are in CR2/CRp2.
研究概览
简要总结
This is an open-label, multicenter, randomized, parallel groups study of Galinpepimut-S (GPS) vs the best available treatment (BAT) in patients with Acute Myeloid Leukemia (AML) in second complete remission (CR2) or in second complete remission with incomplete platelet recovery (CRp2).
All patients will have their historical bone marrow samples and/or peripheral blood samples drawn during screening stained for WT1 via IHC and/or analyzed via PCR by central pathology review. The primary goal of the study will be to demonstrate an advantage for GPS in overall survival in these patient populations. The study will enroll approximately 116 patients and will be conducted at about 100 investigational sites. Patients on the BAT arm may be treated with observation (whereby palliative management of leukocytosis with hydroxyurea is allowed), a hypomethylating agent (decitabine or azacitidine), and/or venetoclax and/or low-dose cytarabine (ara-C). Patients whose remission in CR2 that can be maintained with molecularly targeted agents (e.g. FLT-3 or IDH inhibitors) per investigator’s determination will not be eligible. However, there are no restrictions on prior use of any agents in the CR1 setting. Patients can not receive GPS as an adjunct therapy to any other agents. Patients on the GPS arm will receive 70 μg of sargramostim (GM-CSF) on Day -2 as a single injection and on Day 1 30 – 60 minutes before each injection of GPS. The first two administrations of GM-CSF will take place at the same anatomical site as the planned administration of GPS within each treatment cycle. GPS will be administered as an immunization induction every 2 weeks for 6 administrations (Weeks 0 – 10); this will be followed by a 4-week period of no treatment. Treatment will then resume for 6 administrations as an initial booster phase every 4 weeks (Weeks 14 – 34) which will again be followed by a period of no treatment lasting 6 weeks. GPS will be resumed after this period as a second booster phase and will be administered every 6 weeks for 3 administrations (Weeks 40 – 52). Following each administration of GM-CSF or GPS, patients will be observed for approximately 30 minutes. An End of Treatment visit will be conducted within 30 days following the last dose of GPS. Patients will then enter the long-term follow-up portion of the trial where they will be followed for recurrence of leukemia and survival.
The primary objective of the trial is to compare the efficacy of GPS to the Investigator’s choice of BAT on overall survival in subjects with AML who are in CR2/CRp2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients, or their legally acceptable representatives, must be willing and able to understand and provide signed informed consent for the study that fulfills Institution Review Board (IRB) guidelines
- •Male or female patients > 18 years of age on the day of signing informed consent
- •Subjects must have a diagnosis of AML according to the WHO criteria (primary/de novo or secondary, including treatment-related [e.g., due to prior anthracycline use], as well as cases due to progression of antecedent hematological disorder [e.g., MDS, MPN, or MDS/MPN ‘overlap’ syndrome).
- •Subjects must be in second or later morphological complete remission (with or without platelet recovery; CR2/CRp2) for relapsed AML based on the CRp criteria as follows: a.
- •1000 cells/µL.
- •Peripheral blood platelet count >20,000/µL f.
- •absence of extramedullary disease.
- •Patients must have > 800 lymphocytes/ µL.
- •Patients’ leukemic blasts must express WT1 per either IHC or PCR (See APPENDIX 1 and APPENDIX 3)
- •Subjects must not be candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patient’s preference or lack of an available donor.
- •Subjects must have received the last dose of re-induction antileukemic therapy at least 4 weeks or ten half-lives of induction chemotherapy (whichever is shorter) prior to receiving study treatment.
- •Subjects must be consented within 4 months of having achieved CR2/CRp2 or later.
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, 2 or 3 (See APPENDIX 2: ECOG Performance Status)
- •Subjects must have an estimated life expectancy >6 months.
- •If female, is postmenopausal (at least 12 sequential months of amenorrhea) or surgically sterile.
- •Females of childbearing potential must have a negative pregnancy test.
- •Female patients of childbearing potential who are heterosexually active and male patients with female sexual partners of childbearing potential must agree to use an effective method of contraception (e.g., oral contraceptives, double-barrier methods such as a condom and a diaphragm, intrauterine device) during the study and for 4 months following the last dose of study medication, or to abstain from sexual intercourse for this time; a woman not of childbearing potential is one who has undergone bilateral oophorectomies or who is post menopausal, defined as the absence of menstrual periods for 12 consecutive months.
- •Subjects must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1 after completion of prior AML therapy with the exception of the platelet count requirements (i.e., as long as peripheral blood platelet count is >20,000/µL).
- •Subjects must not have end stage renal disease.
- •Subjects must have adequate hepatic function defined as a serum total bilirubin.
排除标准
- •For subjects randomized to GPS maintenance monotherapy: a.
- •Continuation of any agents administered as part of induction of CR2/CRp2 or later b.
- •Receiving any concurrent anti-AML systemic therapy c.
- •Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).
- •Received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks prior or 10 half lives, whichever is shorter prior to receiving study treatment.
- •Corticosteroids for chronic conditions (at doses ≤10 mg/day of prednisone or equivalent) are permitted, as are inhalational, intra-ocular, intra articular and topical corticosteroids
- •Subjects with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
- •Subjects with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
- •Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study.
- •Subjects who currently have, central nervous system leukemia.
- •Has received a live vaccine within 30 days prior to the first dose of study drug.
- •Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine.
- •Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- •Vaccines for Covid-19 used under an EUA, are considered an authorized (though not an approved or cleared) medical product for use in clinical care.
- •Vaccines used for the prevention of Covid-19 are allowed to be used.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks, or in the case of drugs 10 half lives, whichever is shorter, prior to the first dose of study treatment.
- •Patients who had an SCT after their achieving CR2 or CRp2 or later are not eligible.
- •Patients with prior SCT are allowed only if they had SCT prior to their latest re-induction .
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
- •The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
- •Steroids taken as short-term therapy (≤ 7 days) for antiemesis are permissible.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.
- •Has known active CNS metastases and/or carcinomatous meningitis.
- •Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- •Has known hypersensitivity to Montanide or vaccine adjuvants.
- •Had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF).
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- •Has an active life threatening infection requiring systemic therapy.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- •This includes any serious, intercurrent, chronic, or acute illness, such as cardiac disease (New York Heart Association [NYHA] class III or IV), hepatic disease, or other illness considered by the investigator as an unwarranted high risk for investigational drug treatment.
- •Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 30 days after the last dose of study treatment.
- •Has had an allogeneic tissue/solid organ transplant.
- •Has an active Tuberculosis (TB) or latent TB infection.
结局指标
主要结局
The primary objective of the trial is to compare the efficacy of GPS to Investigators choice of BAT on OS in subjects with AML who are in CR2/CRp2.
时间窗: At day 0, week 2, 4,6,8,10,12,14, 18, 22,26,30,34,40,46,52, End of Treatment, Relapsed, 30d after FU, Long term FU and End of study (GPS arm) | Day 0, week 4, 8,12,14,18,22,26,30,34,40,46,52,EOT,Relapse, LTFU, EOS (BAT arm)
次要结局
- To assess the safety & tolerability of GPS as measured by clinical reporting of adverse events, findings on physical exam and laboratory parameters in subjects with AML who are in CR2/CRp2.(• To evaluate the efficacy of GPS compared to Investigators choice of BAT, in subjects with AML who are in CR2/CRp2, with respect to: o Leukemia Free Survival (LFS) o OS rate (%) at 6, 9 and 12 months (landmark) o LFS rate (%) at 6, 9, and 12 months (landmark) o Minimal residual disease by multigene assay (in both peripheral blood and bone marrow aspirates))