A Study of the Efficacy and Safety of Galinpepimut-S (GPS) for the Treatment of Acute Myeloid Leukemia Compared to Investigator's Choice of Best Available Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sellas Life Sciences Group Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jun 2021 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sellas Life Sciences

External identifiers

EU CT number

2024-516405-23-00

EudraCT number

2019-004134-42

ClinicalTrials.gov

NCT04229979

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To compare the efficacy of GPS to Investigator's choice of Best Available Treatment (BAT) on overall survival (OS) in subjects with AML who are in CR2/CRp2

Secondary objectives 3

1. 1. To assess the safety & tolerability of GPS as measured by clinical reporting of adverse events, findings on physical exam and laboratory parameters in subjects with AML who are in CR2/CRp2.
2. 2. To evaluate the efficacy of GPS compared to Investigator's choice of BAT, in subjects with AML who are in CR2/CRp2, with respect to: o Leukemia Free Survival (LFS) o OS rate (%) at 6, 9 and 12 months (landmark) o LFS rate (%) at 6, 9, and 12 months (landmark) o Minimal residual disease by multigene assay (both in peripheral blood and bone marrow aspirates).
3. 3. To evaluate the effect of prior allogeneic (hematopoietic) stem cell transplantation on the efficacy of GPS compared to Investigator's choice of BAT, in subjects with AML who are in CR2/CRp2, with respect to: o OS and OS rate (%) at specified landmarks o Leukemia Free Survival (LFS) and LFS rate (%) at specified landmarks.

Conditions and MedDRA coding

Acute myeloid leukemia (AML) in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. 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. 2. Male or female patients > 18 years of age on the day of signing informed consent.
3. 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. 4. Les patients doivent être en deuxième rémission morphologique complète ou ultérieure (avec ou sans récupération des plaquettes ; RC2/RCp2) pour une LMA en rechute, selon les critères de RCp suivants : a. < 5 % de myéloblastes dans la moelle osseuse. b. Absence de corps d'Auer. c. Absence de blastes périphériques circulants. d. Nombre absolu de neutrophiles (NAN) du sang périphérique >1000 cellules/µL. e. Numération plaquettaire du sang périphérique >20 000/µL. f. Absence de maladie extra-médullaire.
5. 5. Patients must have > 300 lymphocytes/ µL.
6. 6. Subjects must not be candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patients preference or lack of an available donor.
7. 7. 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.
8. 8. Subjects must be consented within 6 months of having achieved CR2/CRp2 or later.
9. 9. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1,2 or 3.
10. 10. Subjects must have an estimated life expectancy >6 months.
11. 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. 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. 13. 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).
14. 14. Subjects must not have end stage renal disease.
15. 15. Subjects must have adequate hepatic function defined as a serum total bilirubin as a serum total bilirubin <2 x 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. 16. Subjects 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 19

1. 1- For subjects randomized to GPS maintenance monotherapy: a. Continuation of any agents administered as part of induction of CR2/CRp2 or later b. Receiving any concurrent anti-AML systemic therapy c. Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]). d. 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) are 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. 10- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.
3. 11- 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.
4. 2- Subjects with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
5. 3- Subjects with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
6. 4- Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study.
7. 5- Subjects who currently have, central nervous system leukemia
8. 6- 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. 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.
9. 7- Is 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.
10. 8- Pat who had an SCT after their most recent re-induction that resulted in CR2 or CRp2 or later are not eligible. Pat. with prior SCT are allowed only if they had SCT prior to their latest re-induction or achieved CR by means of transplant.
11. 9- 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 systemic 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.
12. 12-Has known hypersensitivity to Montanide or vaccine adjuvants.
13. 13-Had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF)
14. 14-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 is not considered a form of systemic treatment and is allowed.
15. 15-Has an active life threatening infection requiring systemic therapy.
16. 16-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.
17. 17-Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
18. 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. 19-Has had an allogeneic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Median overall survival (OS)

Secondary endpoints 1

1. Leukemia Free Survival (LFS); 6-, 9-, and 12-month OS; 6-, 9-, and 12- month LFS, and presence of MRD.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 6

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sellas Life Sciences Group Inc.

Sponsor organisation

Sellas Life Sciences Group Inc.

Address

7 Times Square Suite 2503

City

New York

Postcode

10036-6550

Country

United States

Scientific contact point

Organisation

Sellas Life Sciences Group Inc.

Contact name

Clinical Development

Public contact point

Organisation

Sellas Life Sciences Group Inc.

Contact name

Clinical Development

Third parties 11

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications