Clinical trial NCT04229979: Galinpepimut-S Versus Investigator's Choice of Best Available Therapy for Maintenance in AML CR2/CRp2
Official title: A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigator's Choice of Best Available Therapy in Subjects With Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second-Line Salvage Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: maintenance
complete remission
overall survival
galinpepimut-S
randomized
Wilms Tumor-1 protein
Lead sponsor: Sellas Life Sciences Group
Sponsor class: INDUSTRY
First posted: 2020-01-18
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, multicenter, randomized, parallel group study
Primary purpose: TREATMENT

Brief summary: To assess the safety and efficacy of galinpepimut-S (GPS) compared with investigator's choice of best available therapy (BAT) on overall survival (OS) in subjects with acute myeloid leukemia (AML) who are in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2).

Detailed description: This is an open-label, multicenter, randomized, parallel groups study of galinpepimut-S (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 and/or peripheral blood drawn during screening stained for WT1 via IHC and/or analyzed via PCR 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 140 patients and will be conducted at about 110 investigational sites. Patients will be randomized 1:1 to GPS or BAT stratified by whether they are in CR2 or CRp2, their cytogenetic risk at diagnosis (poor vs all other), whether they harbor minimal residual disease (MRD), and the duration of CR1 of less than one year or one year or more.

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 and/or 4. low-dose ara-C. Patients whose remission in CR2 can be maintained with molecularly targeted agents (e.g. FLT-3 or IDH inhibitors) per investigator's determination will not be eligible. However, there are no restrictions on prior use of any agents in the CR1 setting. Patients cannot 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 (Weeks 40 until - disease relapse). Following each administration of GM-CSF or GPS, patients will be observed for approximately 30 minutes. 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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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. 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. Must be in second morphological complete remission (with or without platelet recovery; CR2/CRp2) for relapsed AML based upon the CRp criteria as follows:

   1. \<5% myeloblasts in bone marrow
   2. Absence of Auer rods
   3. Absence of circulating peripheral blasts
   4. Peripheral blood absolute neutrophil count (ANC) \>1000 cells/µL
   5. Peripheral blood platelet count \>20,000/µL
   6. Absence of extramedullary disease
5. Patients must have \> 300 lymphocytes/ μL.
6. Must not be candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patient's preference or lack of an available donor.
7. Must have received the last dose of re-induction antileukemic therapy at least 4 weeks or ten half-lives of induction therapy (whichever is shorter) prior to receiving study treatment.
8. Must be consented within 6 months of having achieved CR2/CRp2 or later.
9. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3.
10. Must have an estimated life expectancy \>6 months.
11. If female, is postmenopausal (at least 12 sequential months of amenorrhea) or surgically sterile. Females of childbearing potential must have a negative pregnancy test
12. 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 to 6 months (depending on treatment) 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.
13. 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).
14. Must not have end stage renal disease.
15. 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.
16. Must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required.

Exclusion Criteria:

1. For subjects randomized to GPS maintenance monotherapy:

   1. Continuation of any agents administered as part of induction of CR2/CRp2 or later
   2. Receiving any concurrent anti-AML systemic therapy
   3. Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor \[G-CSF\]).
   4. Received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks prior or 10 half lives, whichever is shorter prior to receiving study treatment. Systemic corticosteroids for chronic conditions (at doses ≤10 mg/day of prednisone or equivalent) or permitted, as are inhalational, intra-ocular, intra-articular and topical corticosteroids as well as any corticosteroids or other immunosuppressive therapies that do not act systemically (e.g. budesonide) at any dose level.
2. Imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
3. Acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
4. Serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject being participating in the clinical study.
5. Currently have, central nervous system leukemia.
6. 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. Vaccines for Covid-19 used under an EUA, are considered an authorized (though not an approved or cleared) medical product for use in clinical care. Vaccines used for the prevention of Covid-19 are allowed to be used.
7. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks, or in the case of drugs 10 half lives, whichever is shorter, prior to the first dose of study treatment.
8. Patients who had an SCT after their most recent re-induction that resulted in CR2 or CRp2 or later are not eligible. Patients with prior SCT are allowed only if they had SCT prior to their latest re-induction or achieved CR by means of transplant ("hot transplant").
9. 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 exceeding 10 mg daily of prednisone equivalent within 7 days prior the first dose of study drug. The use of physiologic doses of corticosteroids and/or immunosuppressive agents may be approved after consultation with the Sponsor. Steroids taken as short-term therapy (≤ 7 days) for antiemesis are permissible.
10. Known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.
11. 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.
12. Known hypersensitivity to Montanide or vaccine adjuvants.
13. Previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF).
14. 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.
15. Active life threatening infection requiring systemic therapy.
16. 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.
17. Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
18. 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.
19. Has had an allogeneic tissue/solid organ transplant.

Primary outcomes:
measure: OS
timeFrame: 5 years
Secondary outcomes:
measure: LFS
timeFrame: 5 years
measure: OS rate (%)
timeFrame: At 6, 9 and 12 months
measure: LFS rate (%)
timeFrame: At 6, 9, and 12 months
measure: MRD
timeFrame: Up to 91 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Hematology and Oncology
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute - SCRI - PPDS
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Rush University Cancer Center
state: Illinois
city: New Orleans
country: United States
facility: Tulane Cancer Center - Liberty
state: Louisiana
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Greenville
country: United States
facility: Bon Secours St. Francis Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Amiens
country: France
facility: CHU Amiens-Picardie - Hopital Sud
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: CHU de Caen
city: Grenoble
country: France
facility: CHU de Grenoble
city: Nantes
country: France
facility: Hôtel Dieu - Nantes
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Rostock
country: Germany
facility: Universitätsklinik Rostock
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupoli
city: Athens
country: Greece
facility: General Hospital of Athens "Evaggelismos"
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Athens
country: Greece
facility: General Hospital of Athens "G. Gennimatas"
city: Athens
country: Greece
facility: General Hospital of Athens "Ηippokration"
city: Chaïdári
country: Greece
facility: University General Hospital "Attikon"
city: Chortiátis
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina
city: Río
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: University General Hospital of Thessaloniki "Ahepa"
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Győr
country: Hungary
facility: Petz Aladár Egyetemi Oktató Kórház
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Kannur
country: India
facility: Malabar Cancer Centre
state: Kerala
city: Hyderabad
country: India
facility: Yashoda Hospital
city: Ludhiāna
country: India
facility: Fortis Hospital
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Patna
country: India
facility: State Cancer Institute, Indira Gandhi Institute of Medical Sciences
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Klinika Hematologii i Transplantologii
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o.
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Legnicy
city: Olsztyn
country: Poland
facility: Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
city: Slomniki
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Cáceres
country: Spain
facility: Hospital de San Pedro de Alcantara
city: Córdoba
country: Spain
facility: C.H. Regional Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Chang Hua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Sellas Life Sciences Group
name: Dragan Cicic Chief Development Officer, MD
role: STUDY_DIRECTOR
References: