Galinpepimut-S Versus Investigator's Choice of Best Available Therapy for Maintenance in AML CR2/CRp2

Phase 3

Active, not recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Biological: Galinpepimut-S; Drug: Azacitidine; Biological: GM-CSF; Drug: Venetoclax; Other: Montanide; Drug: Decitabine; Drug: Cytarabine; Other: Observation

• Registration Number: NCT04229979
• Lead Sponsor: Sellas Life Sciences Group

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 for 3 administrations (Weeks 40 - 52). 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.

Study Timeline

• Study First Submitted: 2020-01-12
• Study First Submitted QC: 2020-01-12
• Study First Posted: 2020-01-18
• Study Start: 2021-02-08
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-08
• Last Update Posted: 2024-04-09
• Primary Completion: 2024-12
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 128

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 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.

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Galinpepimut-S + Montanide + GM-CSF	GM-CSF	A maximum of 15 total injections will be administered as follows: 1. First 6 galinpepimut-S injections: every 2 weeks (Weeks 0 - 10) followed by a 4-week period of no treatment. The first series of 6 injections of galinpepimut-S define the initial immunization induction phase. 2. Injections 7 to 12: every 4 weeks (between Weeks 14 and 34) followed by a 6-week period of no treatment. The second series of injections of galinpepimut-S define the early immune booster phase. 3. Injections 13 to 15: every 6 weeks (between Weeks 40 and 52). The third series of injections of galinpepimut-S define the late immune booster phase. Note: Galinpepimut-S is admixed with Montanide adjuvant before administered as a subcutaneous injection. GM-CSF is administered one day before and on the same day as the galinpepimut-S + Montanide injection.
Galinpepimut-S + Montanide + GM-CSF	Montanide	A maximum of 15 total injections will be administered as follows: 1. First 6 galinpepimut-S injections: every 2 weeks (Weeks 0 - 10) followed by a 4-week period of no treatment. The first series of 6 injections of galinpepimut-S define the initial immunization induction phase. 2. Injections 7 to 12: every 4 weeks (between Weeks 14 and 34) followed by a 6-week period of no treatment. The second series of injections of galinpepimut-S define the early immune booster phase. 3. Injections 13 to 15: every 6 weeks (between Weeks 40 and 52). The third series of injections of galinpepimut-S define the late immune booster phase. Note: Galinpepimut-S is admixed with Montanide adjuvant before administered as a subcutaneous injection. GM-CSF is administered one day before and on the same day as the galinpepimut-S + Montanide injection.
Best Available Therapy	Observation	Four options, as monotherapy or as combination of agents listed below, (per treating investigator's choice): 1. Observation (whereby palliative management with hydroxyurea is allowed), or 2. HMA (decitabine or azacitidine), and/or 3. Venetoclax, and/or 4. Low-dose ara-C
Galinpepimut-S + Montanide + GM-CSF	Galinpepimut-S	A maximum of 15 total injections will be administered as follows: 1. First 6 galinpepimut-S injections: every 2 weeks (Weeks 0 - 10) followed by a 4-week period of no treatment. The first series of 6 injections of galinpepimut-S define the initial immunization induction phase. 2. Injections 7 to 12: every 4 weeks (between Weeks 14 and 34) followed by a 6-week period of no treatment. The second series of injections of galinpepimut-S define the early immune booster phase. 3. Injections 13 to 15: every 6 weeks (between Weeks 40 and 52). The third series of injections of galinpepimut-S define the late immune booster phase. Note: Galinpepimut-S is admixed with Montanide adjuvant before administered as a subcutaneous injection. GM-CSF is administered one day before and on the same day as the galinpepimut-S + Montanide injection.
Best Available Therapy	Venetoclax	Four options, as monotherapy or as combination of agents listed below, (per treating investigator's choice): 1. Observation (whereby palliative management with hydroxyurea is allowed), or 2. HMA (decitabine or azacitidine), and/or 3. Venetoclax, and/or 4. Low-dose ara-C
Best Available Therapy	Azacitidine	Four options, as monotherapy or as combination of agents listed below, (per treating investigator's choice): 1. Observation (whereby palliative management with hydroxyurea is allowed), or 2. HMA (decitabine or azacitidine), and/or 3. Venetoclax, and/or 4. Low-dose ara-C
Best Available Therapy	Decitabine	Four options, as monotherapy or as combination of agents listed below, (per treating investigator's choice): 1. Observation (whereby palliative management with hydroxyurea is allowed), or 2. HMA (decitabine or azacitidine), and/or 3. Venetoclax, and/or 4. Low-dose ara-C
Best Available Therapy	Cytarabine	Four options, as monotherapy or as combination of agents listed below, (per treating investigator's choice): 1. Observation (whereby palliative management with hydroxyurea is allowed), or 2. HMA (decitabine or azacitidine), and/or 3. Venetoclax, and/or 4. Low-dose ara-C

Primary Outcome Measures

Name	Time	Method
Overall survival	Up to 156 weeks	The primary objective of the trial is to compare the efficacy of GPS to Investigator's choice of BAT on OS in subjects with AML who are in CR2/CRp2.

Secondary Outcome Measures

Name	Time	Method
LFS rate (%)	At 6, 9, and 12 months	Percentage of patients surviving and being free of leukemic relapse
MRD	Up to 91 weeks	Minimum residual disease
LFS	Up to 156 weeks	Leukemia free survival
OS rate (%)	At 6, 9 and 12 months	Percentage of patients surviving

Trial Locations

Locations (73)

Mayo Clinic Jacksonville Florida; 🇺🇸 Jacksonville, Florida, United States

CHU de Caen; 🇫🇷 Caen, France

General Hospital of Athens "Evaggelismos"; 🇬🇷 Athens, Greece

Augusta University; 🇺🇸 Augusta, Georgia, United States

Universitätsklinik Rostock; 🇩🇪 Rostock, Germany

Tulane Cancer Center - Liberty; 🇺🇸 New Orleans, Louisiana, United States

Virginia Cancer Specialists; 🇺🇸 Gainesville, Virginia, United States

General Hospital of Athens "Laiko"; 🇬🇷 Athens, Greece

General Hospital of Thessaloniki "G. Papanikolaou"; 🇬🇷 Chortiátis, Greece

Hôtel Dieu - Nantes; 🇫🇷 Nantes, France

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Germany

Universitatsklinikum Leipzig; 🇩🇪 Leipzig, Germany

University General Hospital "Attikon"; 🇬🇷 Chaïdári, Greece

CHU Amiens-Picardie - Hopital Sud; 🇫🇷 Amiens, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Spain

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Baylor Scott and White Research Institute; 🇺🇸 Dallas, Texas, United States

University General Hospital of Alexandroupoli; 🇬🇷 Alexandroupolis, Greece

University General Hospital of Thessaloniki "Ahepa"; 🇬🇷 Thessaloníki, Greece

Yashoda Hospital; 🇮🇳 Hyderabad, India

CHU de Grenoble; 🇫🇷 Grenoble, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Hospital de San Pedro de Alcantara; 🇪🇸 Cáceres, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Clinica Universidad Navarra; 🇪🇸 Pamplona, Spain

General Hospital of Athens "G. Gennimatas"; 🇬🇷 Athens, Greece

University General Hospital of Patras; 🇬🇷 Río, Greece

Petz Aladár Egyetemi Oktató Kórház; 🇭🇺 Győr, Hungary

C.H. Regional Reina Sofia; 🇪🇸 Córdoba, Spain

Pécsi Tudományegyetem; 🇭🇺 Pécs, Hungary

Szpitale Pomorskie Sp. z o.o.; 🇵🇱 Gdynia, Poland

Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy; 🇵🇱 Bydgoszcz, Poland

SP ZOZ Szpital Uniwersytecki w Krakowie; 🇵🇱 Slomniki, Poland

Malabar Cancer Centre; 🇮🇳 Kannur, Kerala, India

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu; 🇵🇱 Wrocław, Poland

Complejo Asistencial Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitari i Politecnic La Fe de Valencia; 🇪🇸 Valencia, Spain

Fortis Hospital; 🇮🇳 Ludhiāna, India

Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii; 🇵🇱 Olsztyn, Poland

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

University of Texas - MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

UCLA Medical Hematology and Oncology; 🇺🇸 Los Angeles, California, United States

The Oncology Institute of Hope and Innovation; 🇺🇸 Whittier, California, United States

Rush University Cancer Center; 🇺🇸 Chicago, Illinois, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Bon Secours St. Francis Cancer Center; 🇺🇸 Greenville, South Carolina, United States

CHU Angers; 🇫🇷 Angers, France

Hôpital Saint Antoine; 🇫🇷 Paris, France

General Hospital of Athens "Ηippokration"; 🇬🇷 Athens, Greece

Changhua Christian Hospital; 🇨🇳 Chang Hua, Taiwan

New York Medical College; 🇺🇸 Valhalla, New York, United States

O'Neal Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Colorado Blood Cancer Institute - SCRI - PPDS; 🇺🇸 Denver, Colorado, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

CHU de Poitiers; 🇫🇷 Poitiers, France

Wojewodzki Szpital Specjalistyczny w Legnicy; 🇵🇱 Legnica, Poland

University General Hospital of Ioannina; 🇬🇷 Ioánnina, Greece

Swietokrzyskie Centrum Onkologii; 🇵🇱 Kielce, Poland

State Cancer Institute, Indira Gandhi Institute of Medical Sciences; 🇮🇳 Patna, India

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Uniwersyteckie Centrum Kliniczne Klinika Hematologii i Transplantologii; 🇵🇱 Gdańsk, Poland

Szpital Wojewodzki w Opolu; 🇵🇱 Opole, Poland

Clinical Centre of Vojvodina; 🇷🇸 Novi Sad, Serbia

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

All India Institute of Medical Sciences; 🇮🇳 New Delhi, India

Instytut Hematologii i Transfuzjologii; 🇵🇱 Warsaw, Poland

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

University Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Kaohsiung Medical University Hospital; 🇨🇳 Kaohsiung, Taiwan

Northwell Health Cancer Institute; 🇺🇸 Lake Success, New York, United States