| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute myeloid leukemia (AML) in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000887 |
| E.1.2 | Term | Acute myeloid leukemia in remission |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary Objective:
The primary objective of the trial is 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.
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
• 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.
• 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)
• 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 OS and OS rate (%) at specified landmarks o Leukemia Free Survival (LFS) and LFS rate (%) at specified landmarks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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. Male or female patients > 18 years of age on the day of signing informed consent.
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. Subjects must be in second or later morphological complete remission (with or without platelet recovery; CR2/CRp2) for relapsed AML based on the CRp criteria as follows:
a.<5% myeloblasts in bone marrow.
b.Absence of Auer rods
c.Absence of circulating peripheral blasts.
d.Peripheral blood absolute neutrophil count (ANC) >1000 cells/µL.
e.Peripheral blood platelet count >20,000/µL
f.Absence of extramedullary disease.
5. Patients must have > 300 lymphocytes/ µL.
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. 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. Subjects must be consented within 6 months of having achieved CR2/CRp2 or later.
9. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1,2 or 3.
10. Subjects 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. 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. Subjects must not have end stage renal disease.
15. Subjects 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. Subjects must be willing and able to return to the clinical site for adequate follow-up and to comply with the protocol as required. |
|
| E.4 | Principal exclusion criteria |
1. For subjects randomized to GPS maintenance monotherapy:
•Continuation of any agents administered as part of induction of CR2/CRp2 or later
• Receiving any concurrent anti-AML systemic therapy
•Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).
•Received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks 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 at any dose level.
2. Subj. with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor). 3. Subj. with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
4. Subj. 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. Subj. 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 stem cell transplant (SCT) after their most recent reinduction that result in CR2 or CRp2 or later are not eligible.Pat. with
prior SCT are allowed only if they had SCT prior to their latest
reinduction 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
1st dose of study drug. The use of physiologic doses of corticosteroids
and/or other immunosuppressive agents may be approved after
consultation with the Sponsor. Steroids taken as short-term therapy (≤ 7
days) for antiemesis are permissible.
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.
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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Median overall survival (OS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At every contact with the patient; continuously throughout the trial. |
|
| E.5.2 | Secondary end point(s) |
| Leukemia Free Survival (LFS); 6-, 9-, and 12-month OS; 6-, 9-, and 12-month LFS, and presence of MRD. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 6-, 9-, and 12-month OS; 6-, 9-, and 12-month LFS |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Taiwan |
| China |
| India |
| Serbia |
| United States |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LPLV is understood as last patient last visit to the study site for final study procedures. The sponsor may decide to terminate the study at any time if the external independent data monitoring committee (IDMC) concluded during the risk to subjects outweighs the benefit or if the IDMC concluded the study has reached futility. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
