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 their historical 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), and/or 3. Venetoclax and/or 4. low-dose ara-C. Patients whose
remission in CR2 that can be maintained with other agents (e.g. FLT-3 or IDH
inhibitors) 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
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.
To ensure a comparable level of observation, patients randomized to the BAT arm
will be seen every 4 weeks through Week 52. The Schedules of Procedures for both
the GPS and the BAT arms can be found in Section 6 of the protocol.
All patients will undergo bone marrow aspirates and biopsies at screening, Week 12
and end of treatment. Bone marrow examinations will then be repeated as clinically
indicated. Patients will be assessed for safety at each clinic encounter. The primary
endpoint will be overall survival.