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

Acute Myeloid Leukemia Clinical Trial

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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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04229979
• Other study ID #: SLSG18-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 8, 2021
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Sellas Life Sciences Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 128
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• Galinpepimut-S
Galinpepimut-S admixed with the adjuvant Montanide following specified schedule

Drug:
• Azacitidine
injection
• Venetoclax
tablet
• Decitabine
injection
• Cytarabine
injection

Other:
• Observation
palliative management

Biological:
• GM-CSF
subcutaneous injection

Other:
• Montanide
adjuvant

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sellas Life Sciences Group

Countries where clinical trial is conducted

United States,  France,  Germany,  Greece,  Hungary,  India,  Poland,  Serbia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	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.	Up to 156 weeks
Secondary	LFS	Leukemia free survival	Up to 156 weeks
Secondary	OS rate (%)	Percentage of patients surviving	At 6, 9 and 12 months
Secondary	LFS rate (%)	Percentage of patients surviving and being free of leukemic relapse	At 6, 9, and 12 months
Secondary	MRD	Minimum residual disease	Up to 91 weeks