Efficacy and Safety of Galinpepimut-S Versus Best Available Therapy in Acute Myeloid Leukemia Patients in Second or Later Complete Remission
- Trial ID
- 2024-516405-23-00
- Protocol
- SLSG18-301
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of Galinpepimut-S (GPS) to the Investigator's choice of Best Available Treatment (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). This is clinically relevant as it aims to determine the most effective maintenance therapy to prolong survival in this patient population.
Secondary objectives include:
- Assessing the safety and tolerability of GPS, as measured by clinical reporting of adverse events, findings on physical examination, and laboratory parameters in subjects with AML in CR2/CRp2.
- Evaluating the efficacy of GPS compared to Investigator's choice of BAT with respect to Leukemia Free Survival (LFS), OS rate at 6, 9, and 12 months, LFS rate at 6, 9, and 12 months, and minimal residual disease by multigene assay in both peripheral blood and bone marrow aspirates.
- Evaluating the effect of prior allogeneic (hematopoietic) stem cell transplantation on the efficacy of GPS compared to Investigator's choice of BAT, with respect to OS and OS rate at specified landmarks, and LFS and LFS rate at specified landmarks.
Participants
The clinical trial involves a total of **70 participants** diagnosed with **acute myeloid leukemia (AML)** in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2). The study population includes both male and female subjects, all of whom are over the age of 18. Participants were selected based on their diagnosis of AML according to WHO criteria and their current remission status. The trial includes individuals who are not candidates for allogeneic stem cell transplant due to medical conditions, personal preference, or lack of an available donor. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, and an estimated life expectancy of more than six months. The trial population is required to have adequate hepatic function and must not have end-stage renal disease. Lifestyle considerations such as diet and physical activity are not specified, but participants must be willing to comply with the study protocol and return for follow-up visits. The trial includes a vulnerable population, and all participants or their legally acceptable representatives must provide informed consent in accordance with Institutional Review Board (IRB) guidelines.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **Galinpepimut-S** (GPS) as a maintenance monotherapy compared to the investigator's choice of best available therapy in subjects with **acute myeloid leukemia** (AML) who have achieved complete remission after second-line salvage therapy. This is a randomized, open-label study with a primary objective to compare the efficacy of GPS to the investigator's choice of best available treatment on overall survival in subjects with AML in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2). The trial is expected to run until June 2026, with recruitment having started in September 2021.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, diagnosis, and health status. Follow-up visits will be scheduled to monitor the participants' health, treatment response, and any adverse events. The end-of-study visit will conclude the trial for each participant, where final assessments will be conducted. The expected length of participant involvement is up to 36 months, depending on individual response and health status.
Participants may be withdrawn from the study early if they experience significant adverse effects, if their disease progresses, or if they choose to withdraw consent. The study will adhere to rigorous ethical standards, ensuring that all participants provide informed consent and that their health and safety are prioritized throughout the trial duration.
Treatment
The clinical trial involves the administration of several experimental and comparator medications. **Azacitidine Accord** is provided as a 25 mg/mL powder for suspension for injection. It is administered via **subcutaneous use** with a maximum daily dose of 75 mg/m² and a total dose of 20475 mg/m² over a treatment period of 36 months. The formulation is chemically derived and is manufactured by Accord Healthcare S.L.U. The product is specifically labeled and packaged for clinical trial use.
**Sargramostim (GM-CSF)** is administered as an injection with a maximum daily dose of 70 µg. The total dose is 4340 µg over a 36-month period. This protein-based medication is administered subcutaneously and is provided by Sellas Life Sciences. It is not a pediatric formulation and is used as an auxiliary treatment in the trial.
**Alexan**, containing the active substance **cytarabine**, is available as a 20 mg/mL solution for injection or infusion. It is administered either intravenously or subcutaneously, with a maximum daily dose of 1 mg/kg and a total dose of 312 mg/kg over 36 months. This chemical-based product is manufactured by Sandoz Hungária Kft and is used as a comparator in the trial.
**Galinpepimut-S** is provided as a powder for injection, with a maximum daily dose of 0.8 mg and a total dose of 24.8 mg over the course of 36 months. It is administered subcutaneously and is a mixture-based formulation. This orphan drug is manufactured by Sellas Life Sciences and is the primary test product in the trial.
**Vidaza**, another formulation of **azacitidine**, is available as a 25 mg/mL powder for suspension for injection. It is administered subcutaneously with a maximum daily dose of 75 mg/m² and a total dose of 20475 mg/m² over 36 months. This chemical-based product is manufactured by Bristol-Myers Squibb Pharma EEIG and is used as a comparator in the trial.
**Venclyxto**, containing the active substance **venetoclax**, is provided as 100 mg film-coated tablets. It is administered orally with a maximum daily dose of 400 mg and a total dose of 438 mg over a 36-month period. This chemical-based product is manufactured by AbbVie Deutschland GmbH & Co. KG and is used as a comparator in the trial.
**Dacogen**, containing the active substance **decitabine**, is available as a 50 mg powder for concentrate for solution for infusion. It is administered via intravascular use with a maximum daily dose of 20 mg/m² and a total dose of 3900 mg/m² over 36 months. This chemical-based product is manufactured by Janssen-Cilag International NV and is used as a comparator in the trial.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary endpoint of **median overall survival (OS)** in subjects with acute myeloid leukemia (AML) who have achieved complete remission after second-line salvage therapy. Secondary endpoints include **leukemia-free survival (LFS)**, as well as 6-, 9-, and 12-month OS and LFS, and the presence of minimal residual disease (MRD). These endpoints will provide a comprehensive evaluation of the treatment's impact on patient survival and disease progression.
Inclusion and Exclusion Criteria
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).
- 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.
- Patients must have > 300 lymphocytes/ µL.
- 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.
- 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 6 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 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.
- 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 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.
- 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
- 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.
- 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.
- 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.
- 2- Subjects with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
- 3- Subjects with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
- 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.
- 5- Subjects who currently have, central nervous system leukemia
- 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.
- 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.
- 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.
- 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-Has known hypersensitivity to Montanide or vaccine adjuvants.
- 13-Had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF)
- 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-Has an active life threatening infection requiring systemic therapy.
- 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-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-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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 03 Sept 2021 | 28 |
 Germany | Not Recruiting | 03 Sept 2021 | 11 |
 Greece | Not Recruiting | 03 Sept 2021 | 40 |
 Italy | Not Recruiting | 03 Sept 2021 | 7 |
 Spain | Not Recruiting | 03 Sept 2021 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Azacitidine Accord 25 mg/mL powder for suspension for injection | Comparator | POWDER FOR SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 75 | 36 | PRD9618180 |
SargramostimGM-CSF | Other | INJECTION | SUBCUTANEOUS | 70 | 36 | PRD11466865 |
Alexan 20 mg/ml oldatos injekció vagy infúzió | Comparator | OLDATOS INJEKCIÓ VAGY INFÚZIÓ | INTRAVENOUS (IV) OR SUBCUTANEOUS (SC) | 1 | 36 | PRD896254 |
Galinpepimut-S | Test | POWDER FOR INJECTION | SUBCUTANEOUS | 0.8 | 36 | PRD8193379 |
Vidaza 25 mg/ml powder for suspension for injection | Comparator | POWDER FOR SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 75 | 36 | PRD9244549 |
Venclyxto 100 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 400 | 36 | PRD6353842 |
Dacogen 50 mg powder for concentrate for solution for infusion. | Comparator | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVASCULAR USE | 20 | 36 | PRD649806 |
Azacitidine Accord 25 mg/mL powder for suspension for injection | Comparator | POWDER FOR SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 75 | 36 | PRD7890454 |