A Study to Evaluate the Safety and Effectiveness of Galinpepimut-S Compared to Investigator's Choice of Best Available Therapy to Treat Patients with Acute Myeloid Leukemia

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.

Inclusion Criteria:

  • 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:
    • < 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 > 20,000/µL;
    • Absence of extramedullary disease.
  • Patients must have > 800 lymphocytes/ µL.
  • Patients’ leukemic blasts must express WT1 per IRS scoring system.
  • Subjects must not be candidates atthe time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patients 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.
  • 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 sexualintercourse for this time; a woman not of childbearing potentialis 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 < 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.
  • Subjects must be willing and able to return to the clinical site for adequate followup 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/CRp2 or later;
    • Receiving any concurrent anti-AML systemic therapy;
    • Prior clinically significant allergic reaction to Montanide, sargramostim (GMCSF) 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 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, intraocular, 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 being 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.
    • Is 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.
    • Patients who had an SCT after their achieving CR2 or CRp2 or later are not eleigible. 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.
    • Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
  • 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.

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.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20492951

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