GPS Compared With BAT In AML CR2/CR2p

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

2. Male or female patients > 18 years of age on the day of signing informed consent

3. 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).

4. Subjects must be in second morphological complete remission (with or without

platelet recovery; CR2/CRp2) for relapsed AML based on the CRp criteria as

follows:

a. <5% myeloblasts in bone marrow.

b. Absence of Auer rods

c. Absence of circulating peripheral blasts.

d. Peripheral blood absolute neutrophil count (ANC) >1000 cells/μL.

e. Peripheral blood platelet count >60,000/μL

f. Absence of extramedullary disease.

5. Patients must have > 800 lymphocytes/ μL.

6. Patients’ leukemic blasts must express WT1 per IRS scoring system (See

APPENDIX 1: WT1 IHC Assessment and Documentation)

7. Subjects must be free of any requirement for red blood cell transfusions.

8. Subjects must not be 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.

9. Subjects must have received the last dose of induction antileukemic therapy at

least 3 months prior to study enrolment.

10. Subjects must be consented within 4 months of having achieved CR2/CRp2

11. Subjects must have an Eastern Cooperative Oncology Group (ECOG)

performance status of 0,1 or 2 (See APPENDIX 2: ECOG Performance Status)

12. Subjects must have an estimated life expectancy >6 months.

13. If female, is postmenopausal (at least 12 sequential months of amenorrhea) or

surgically sterile. Females of childbearing potential must have a negative

pregnancy test

14. 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.

15. 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 >60,000/μL).

16. Subjects must 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.

17. Subjects must 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.

18. Subjects must be willing and able to return to the clinical site for adequate followup

and to comply with the protocol as required.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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