E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukemia NOS |
|
E.1.1.1 | Medical condition in easily understood language |
Acute Myeloid Leukemia NOS |
|
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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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 |
Measure the proportion of patients who develop binding and neutralizing antibodies in the blood after treatment with sargramostim following induction/reinduction chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
Assess the time after treatment at which the antibodies develop and the level of
antibodies is measured after the first dose.
Measure the levels of immunoglobulin protein.
Assess the impact of any immune response on safety and the duration of low
white blood cell count. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Able to provide informed consent.
Newly diagnosed acute myeloid leukemia (AML) to be treated with standard of care induction chemotherapy as per local policy.
Patients 55 to 70 years of age (inclusive).
Negative serum pregnancy test within 30 days prior to receiving the first dose of induction
chemotherapy in female participants who are <2 years postmenopausal or who are of childbearing potential and have agreed to begin or continue using an adequate method of contraception. |
|
E.4 | Principal exclusion criteria |
Prior treatment with sargramostim or any leukocyte growth factor (LGF) product.
Prior myelodysplastic syndrome (MDS).
Known central nervous system (CNS) leukemic involvement diagnosed by cytologic findings in cerebrospinal fluid and/or by computed tomography (CT) or magnetic resonance imaging (MRI).
Out of range (>2x normal) laboratory values.
Clinically important medical conditions unrelated to AML as determined by the Investigator.
Eastern Cooperative Oncology Group (ECOG) performance status >2.
Bone marrow blasts ≥5% on marrow examination following induction or reinduction chemotherapy.
History of allergy to yeast products, recombinant human granulocyte/macrophage-colony-stimulating factor, or any component of sargramostim. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
a) Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies)
b) Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies)
c) Proportion of patients who develop antibodies (binding antibodies
and neutralizing antibodies)
d) Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
a) 1 month after 1st dose of sargramostim
b) 2 months after 1st dose of sargramostim
c) 3 months after 1st dose of sargramostim
d) 6 months after 1st dose of sargramostim. If positive at month 6, this will be continued every 6 months until the values return to baseline or up to 24 months |
|
E.5.2 | Secondary end point(s) |
a) Assessment of antibodies (antibody detection and antibody titers)
b) Assessment of antibodies (antibody detection and antibody titers)
c) Assessment of antibodies (antibody detection and antibody titers)
d) Assessment of antibodies (antibody detection and antibody titers)
e) Assessment of immunoglobulin levels
f) Assessment of immunoglobulin levels
g) Assessment of immunoglobulin levels
h) Assessment of immunoglobulin levels
i) Proportion of patients with adverse events
l) Duration of neutropenia (time from initiation of sargramostim to recovery of ANC to ≥1500/mm^3) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) 1 month after 1st dose of sargramostim
b) 2 months after 1st dose of sargramostim
c) 3 months after 1st dose of sargramostim
d) 6 months after 1st dose of sargramostim. If positive at month 6, this will be continued
every 6 months until the values return to baseline up to 24 months
e) 1 month after 1st dose of sargramostim
f) 2 months after 1st dose of sargramostim
g) 3 months after 1st dose of sargramostim
h) 6 months after 1st dose of sargramostim. If
antibodies are positive at month 6, the level of immunoglubolins will be assesed every 6
months until the antibodies level return to baseline or up to 24 months
i) Up to 24 months
l) Up to 42 days after first day of sargramostim administration
|
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Brazil |
Bulgaria |
Croatia |
Czech Republic |
Hungary |
Italy |
Romania |
Russian Federation |
Serbia |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |