Open Label Study of Sargramostim Among Patients Receiving Myelosuppressive Induction Chemotherapy for Acute Myelogenous Leukemia

Study Overview
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Brief Summary
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Primary Objective: Measure the proportion of patients who develop binding and neutralizing antibodies in the blood after treatment with sargramostim following induction/reinduction chemotherapy. Secondary Objectives: 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.

Detailed Description
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The total study duration for a participant is up to 6 months from 1st dose of sargramostim or until the antibodies level return to baseline or up to 24 months if antibodies test is positive at month 6.

Official Title
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A Phase II Open Label Study of Sargramostim Among Patients Receiving Myelosuppressive Induction Chemotherapy for Acute Myelogenous Leukemia

Conditions
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Acute Myeloid Leukemia NOS

Intervention / Treatment
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* Drug: sargramostim GZ402664


Participation Criteria
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Eligibility Criteria
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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. 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. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sargramostim<br>Sargramostim is administered daily until the absolute neutrophil count (ANC) equals or exceeds 1500/mm^3 for 3 consecutive measurements or up to 42 days post-induction chemotherapy. | Drug: sargramostim GZ402664<br>* Pharmaceutical form: lyophilized powder in vial Route of administration: subcutaneous<br>* Other names: Leukine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies) |  | 1 month after 1st dose of sargramostim | 
| Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies) |  | 2 months after 1st dose of sargramostim | 
| Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies) |  | 3 months after 1st dose of sargramostim | 
| Proportion of patients who develop antibodies (binding antibodies and neutralizing antibodies) |  | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of antibodies (antibody detection and antibody titers) |  | 1 month after 1st dose of sargramostim | 
| Assessment of antibodies (antibody detection and antibody titers) |  | 2 months after 1st dose of sargramostim | 
| Assessment of antibodies (antibody detection and antibody titers) |  | 3 months after 1st dose of sargramostim | 
| Assessment of antibodies (antibody detection and antibody titers) |  | 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 | 
| Assessment of immunoglobulin levels |  | 1 month after 1st dose of sargramostim | 
| Assessment of immunoglobulin levels |  | 2 months after 1st dose of sargramostim | 
| Assessment of immunoglobulin levels |  | 3 months after 1st dose of sargramostim | 
| Assessment of immunoglobulin levels |  | 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 | 
| Proportion of patients with adverse events |  | Up to 24 months | 
| Duration of neutropenia (time from initiation of sargramostim to recovery of ANC to ≥1500/mm^3) |  | Up to 42 days after first day of sargramostim administration |