This is an open-label, multicenter, randomized, parallel groups study of GPS vs. best
available treatment (BAT) in patients with AML in second complete remission (CR2) or in
second complete remission with incomplete platelet recovery (CRp2). All patients will have
bone marrow samples stained for WT1 via IHC 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 up to
50 investigational sites. Patients will be randomized 1:1 to GPS or BAT stratified by whether
they are in CR2 or CRp2.
Patients on the BAT arm may be treated with 1. observation (whereby palliative management
with hydroxyurea is allowed), 2. a hypomethylating agent (decitabine or azacitidine), 3.
Venetoclax monotherapy or 4. low-dose ara-C monotherapy. Patients whose remission is
maintained with other agents (e.g. FLT-3 or IDH inhibitors) will not be eligible.
Patients on the GPS arm will receive 70 μg of sargramostim (GM- CSF) on Day -2 and Day 1
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 remain in the
clinic for approximately 30 minutes for observation. An End of Treatment visit will be
conducted 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
overall survival.
Inclusion Criteria:
- 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
- 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).
- Must be in second morphological complete remission (with or without platelet recovery;
CR2/CR2p) for relapsed (but not refractory AML) based upon the International Working
Group (IWG) 2003 criteria as follows:
- <5% myeloblasts in bone marrow.
- Absence of circulating peripheral blasts.
- Peripheral blood absolute neutrophil count (ANC) >1000 cells/µL. d. Peripheral
blood platelet count >60,000/µL
- absence of extramedullary disease.
- Leukemic blasts must express WT1
- 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.
- Received the last dose of antileukemic therapy at least 3 months prior to study
enrolment.
- Must be within 3 months of having achieved CR2/CR2p
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- 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.
- 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).
- 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.
- 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.
- Willing and able to return to the clinical site for adequate follow-up and to comply
with the protocol as required.
Exclusion Criteria:
- For subjects randomized to GPS maintenance monotherapy:
- Continuation of any agents administered as part of induction of CR2/CR2p
- Receiving any concurrent anti-AML systemic therapy
- Prior clinically significant allergic reaction to Montanide, sargramostim
(GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).
- Received any 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.
- Complete remission with incomplete hematologic recovery (CRi).
- Complete remission with partial haematologic recovery (CRh).
- Imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with
any degree of match donor).
- Acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
- Serious concurrent illness that in the opinion of the Investigator would pose an undue
risk to the subject being participating in the clinical study.
- History of, or who currently have, central nervous system leukemia.
- Received a live vaccine within 30 days prior to the first dose of study drug.
- Currently participating in or has 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.
- Undergone prior allogeneic hematopoietic stem cell transplantation
- 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.
- Additional malignancy that is progressing or has required active treatment within the
past 5 years, even if currently inactive or unapparent.
- 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.
- Hypersensitivity to Montanide or vaccine adjuvants.
- Previous clinically significant systemic allergic reaction to Montanide, sargramostim
(GM-CSF), or filgrastim (G-CSF).
- 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.
- Active infection requiring systemic therapy.
- 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.20.Has a known psychiatric or substance abuse disorder that would interfere
with the participant's ability to cooperate with the requirements of the study.
- 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.
- Had an allogeneic tissue/solid organ transplant.
- Received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (excluding GM-CSF, but including G CSF or
recombinant erythropoietin) within 4 weeks prior to first study treatment.
