Clinical Trial TitleA Randomized, Open-Label Study of the Efficacy & Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigator's Choice of Best Available Therapy in Subjects with AML Who Have Achieved Complete Remission After Second-Line Salvage Therapy
National Clinical Trial Number:NCT04229979
Clinical Trial Protocol Description:
The main purpose of this study is to compare the effectiveness of study drug, Galinpepimut-S (GPS), with the study doctor’s choice of best available therapy (BAT) on the overall survival rate in patients with acute myeloid leukemia (AML), who are in second complete remission or second complete remission with incomplete platelet recovery. The study also aims to determine how safe GPS is, and whether any of its side effects can be tolerated by patients. The investigational drug, GPS, is a therapeutic cancer vaccine designed to stimulate the immune system to destroy recurrent cancer cells that overproduce Wilm's tumor protein (WT1). This should help to prolong the rate of remission and survival.
Clinical Trial Eligibility Criteria:
In order to participate you must meet the following criteria:
- Are willing and able (or have an able, legally acceptable representative) to understand and provide signed informed consent for the study that fulfills Institution Review Board (IRB) guidelines.
- Are a male or female patient > 18 years of age on the day of signing informed consent.
- 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).
- Are in second morphological complete remission (with or without platelet recovery; CR2/CRp2) for relapsed AML based on the CRp criteria as follows:
- <5% myeloblasts in bone marrow
- Absence of Auer rods
- Absence of circulating peripheral blasts
- Peripheral blood absolute neutrophil count (ANC) >1000 cells/μL
- Peripheral blood platelet count >60,000/μL
- Absence of extramedullary disease
- Have > 800 lymphocytes/ μL.
- Have leukemic blasts that express WT1 per IRS scoring system.
- Are free of any requirement for red blood cell transfusions.
- Are not candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions or lack of an available donor.
- Have received the last dose of induction antileukemic therapy at least 3 months prior to study enrolment.
- Are consented within 4 months of having achieved CR2/CRp2.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2,
- Have an estimated life expectancy >6 months.
- If female, are 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 postmenopausal, defined as the absence of menstrual periods for 12 consecutive months.
- 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 >60,000/μL).
- Have adequate renal function defined as a serum creatinine <2 × upper limit of normal (ULN) or calculated creatinine clearance > 30 mL/min based on the Cockroft-Gault equation.
- Have adequate hepatic function defined as a serum total bilirubin <2 × ULN (except for Gilbert’s syndrome, which will allow bilirubin ≤3.0 mg/dL), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN.
- Are willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required.
You will be excluded from the study if any of the following criteria apply to you:
- For subjects randomized to GPS maintenance monotherapy:
- Have continuation of any agents administered as part of induction of CR2/CRp2.
- Are receiving any concurrent anti-AML systemic therapy.
- Have prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).
- Have received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks prior to enrolment within the study. Corticosteroids for chronic conditions (at doses ≤7.5 mg/day of prednisone or equivalent) or permitted, as are inhalational, intra-ocular, intra-articular and topical corticosteroids.
- Have an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
- Have acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
- Have a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject being participating in the clinical study.
- Have a history of, or who currently have, central nervous system leukemia.
- Have 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.
- Are currently participating in or have participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Have an SCT after their achieving CR2 or CRp2 are not eligible. Patients with prior SCT are allowed only if they had SCT after CR1.
- Have 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.
- Have a known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.
- Have 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.
- Have known hypersensitivity to Montanide or vaccine adjuvants.
- Have had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF).
- Have 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.
- Have an active infection requiring systemic therapy.
- Have 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.
- Have a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
- Are 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.
- Have had an allogeneic tissue/solid organ transplant.
- Have received transfusion of blood products (including platelets or red blood cells) within 2 weeks.
- Have had administration of colony stimulating factors (excluding GM-CSF, but including G-CSF or recombinant erythropoietin) within 4 weeks prior to first study treatment.
This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.