Leukine (Sargramostim) - Summary

LEUKINE SUMMARY

LEUKINE® (sargramostim) is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. GM-CSF is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells. LEUKINE is a glycoprotein of 127 amino acids characterized by 3 primary molecular species having molecular masses of 19,500, 16,800 and 15,500 daltons. The amino acid sequence of LEUKINE differs from the natural human GM-CSF by a substitution of leucine at position 23, and the carbohydrate moiety may be different from the native protein. Sargramostim has been selected as the proper name for yeast-derived rhu GM-CSF.

Use Following Induction Chemotherapy in Acute Myelogenous Leukemia LEUKINE is indicated for use following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. The safety and efficacy of LEUKINE have not been assessed in patients with AML under 55 years of age.

The term acute myelogenous leukemia, also referred to as acute non-lymphocytic leukemia (ANLL), encompasses a heterogeneous group of leukemias arising from various non-lymphoid cell lines which have been defined morphologically by the French-American-British (FAB) system of classification.

Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progenitor Cells LEUKINE is indicated for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. Mobilization allows for the collection of increased numbers of progenitor cells capable of engraftment as compared with collection without mobilization. After myeloablative chemotherapy, the transplantation of an increased number of progenitor cells can lead to more rapid engraftment, which may result in a decreased need for supportive care. Myeloid reconstitution is further accelerated by administration of LEUKINE following peripheral blood progenitor cell transplantation.

Use in Myeloid Reconstitution After Autologous Bone Marrow Transplantation LEUKINE is indicated for acceleration of myeloid recovery in patients with non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin's disease undergoing autologous bone marrow transplantation (BMT). After autologous BMT in patients with NHL, ALL, or Hodgkin's disease, LEUKINE has been found to be safe and effective in accelerating myeloid engraftment, decreasing median duration of antibiotic administration, reducing the median duration of infectious episodes and shortening the median duration of hospitalization. Hematologic response to LEUKINE can be detected by complete blood count (CBC) with differential performed twice per week.

Use in Myeloid Reconstitution After Allogeneic Bone Marrow Transplantation LEUKINE is indicated for acceleration of myeloid recovery in patients undergoing allogeneic BMT from HLA-matched related donors. LEUKINE has been found to be safe and effective in accelerating myeloid engraftment, reducing the incidence of bacteremia and other culture positive infections, and shortening the median duration of hospitalization.

Use in Bone Marrow Transplantation Failure or Engraftment Delay LEUKINE is indicated in patients who have undergone allogeneic or autologous bone marrow transplantation (BMT) in whom engraftment is delayed or has failed. LEUKINE has been found to be safe and effective in prolonging survival of patients who are experiencing graft failure or engraftment delay, in the presence or absence of infection, following autologous or allogeneic BMT. Survival benefit may be relatively greater in those patients who demonstrate one or more of the following characteristics: autologous BMT failure or engraftment delay, no previous total body irradiation, malignancy other than leukemia or a multiple organ failure (MOF) score

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NEWS HIGHLIGHTS

Media Articles Related to Leukine (Sargramostim)

SARGRAMOSTIM-INJECTION, Leukine
Source: MedicineNet Peripheral Blood Stem Cell Transplant Specialty [2005.03.02]
Title: SARGRAMOSTIM-INJECTION, Leukine
Category: Medications Second Source
Created: 3/2/2005
Last Editorial Review: 3/2/2005

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Published Studies Related to Leukine (Sargramostim)

Perioperative sargramostim (recombinant human GM-CSF) induces an increase in the level of soluble VEGFR1 in colon cancer patients undergoing minimally invasive surgery. [2007.12]
INTRODUCTION: Experimentally, laparotomy is associated with increased tumor growth. In humans, abdominal surgery is associated with immunosuppression and elevated plasma VEGF levels that might stimulate tumor growth early after surgery. Avoidance of these surgery-related changes and their consequences may be advantageous. Granulocyte-macrophage colony stimulating factor (GMCSF) is a non-specific immune system up-regulator that has also been associated, experimentally, with increased release of soluble VEGF Receptor 1 (sVEGFR1) which is an endogenous inhibitor of VEGF. This study's purpose was to determine the impact of perioperatively administered recombinant human GMCSF (rhu-GMCSF) on both immune function and plasma sVEGFR1 levels in colorectal cancer patients... CONCLUSIONS: Perioperative GMCSF was not associated with an immune function benefit in this study, however, such treatment leads to increased plasma sVEGFR1 levels. Colorectal resection, with or without GMCSF, was also associated with increased VEGF levels postoperatively. Increased plasma levels of sVEGFR1 after surgery might limit the pro-angiogenic tumor stimulatory effects of VEGF. Further study of GMCSF's impact on angiogenesis appears warranted.

Sargramostim for active Crohn's disease. [2005.05.26]
BACKGROUND: Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have activity in Crohn's disease. To evaluate this novel therapeutic approach, we conducted a randomized, placebo-controlled trial... CONCLUSIONS: This study was negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the quality of life in patients with active Crohn's disease. Copyright 2005 Massachusetts Medical Society.

Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy. [2002.01]
Filgrastim alone and sequential sargramostim and filgrastim have been shown to be more effective than sargramostim alone in the mobilization of CD34(+) cells after myelosuppressive chemotherapy (MC). We sought to compare costs and resource use associated with these regimens... Filgrastim alone and sequential sargramostim and filgrastim are less costly than sargramostim alone after MC, as well as therapeutically more beneficial.

Mobilization of peripheral blood stem cells following myelosuppressive chemotherapy: a randomized comparison of filgrastim, sargramostim, or sequential sargramostim and filgrastim. [2001.05]
Myelosuppressive chemotherapy is frequently used for mobilization of autologous CD34(+) progenitor cells into the peripheral blood for subsequent collection and support of high-dose chemotherapy. The administration of myelosuppressive chemotherapy is typically followed by a myeloid growth factor and is associated with variable CD34 cell yields and morbidity...

Phase III study of granulocyte-macrophage colony-stimulating factor in advanced HIV disease: effect on infections, CD4 cell counts and HIV suppression. Leukine/HIV Study Group. [2000.03.10]
OBJECTIVE: To evaluate the effect of adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim, yeast-derived recombinant human GM-CSF) on incidence and time to opportunistic infection or death, plasma HIV-RNA, and CD4 cell count in patients with advanced HIV disease... CONCLUSIONS: GM-CSF significantly increased CD4 cell count and decreased virological breakthrough and overall infection rate in subjects with advanced HIV disease.

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Clinical Trials Related to Leukine (Sargramostim)

Randomized Phase 2 Trial of Pre-Chemotherapy Leukine Vs. Leukine-Dexamethasone in Combination With Gemzar & 5-FU in Patients With Metastatic Renal Cell Carcinoma [Withdrawn]

- Overall study design: A randomized Phase II study in patients with metastatic RCC Patients

will receive chemotherapy with gemcitabine and 5-FU. Prior to each chemotherapy the patient will receive a combination of Leukine alone (study cohort 1) or Leukine-dexamethasone (study cohort 2).

- Chemotherapy: gemcitabine 1. 0 g/m2 intravenously (infused in the vein)over 30 minutes on

Days 7 and 21, Folinic acid 200 mg/m2 on Days 7-8 and 21-22, then 5-FU 400 mg/m2, intravenously (infused in the vein) over 30 minutes followed by 5-FU 600 mg/m2 intravenously (infused in the vein) over 24 hours.

•Study drugs:

- Cohort 1, Leukine, 250 ug/m2 daily (8 am) subcutaneously (under the skin) on days 1, 2,

3, 4, 5 and 15, 16, 17, 18, and 19;

- Cohort 2, Leukine, 250 ug/m2 daily (8 am) subcutaneously (under the skin)on days 1, 2,

3, 4, 5, and 15, 16, 17, 18, and 19 and dexamethasone 12 mg every 12 hours (8 am and 8 pm) orally (by mouth) on days 3, 4, 5, 6, 7, 17, 18, 19, 20, and 21.

Immuno-Augmentation With GM-CSF of Pneumococcal Vaccine in Chronic Lymphocytic Leukemia Patients [Active, not recruiting]
Primary Objective:

1. To evaluate efficacy of GM-CSF-mediated enhanced seroconversion (protective anti-pneumococcal serum immunoglobulins) in patients receiving conventional 23-valent capsular polysaccharide pneumococcal vaccine (PPV) and 7-valent Pneumococcal conjugated vaccine (PCV7) while undergoing treatment for advanced chronic lymphocytic leukemia (CLL).

Secondary Objective:

1. To evaluate the effect of GM-CSF on the dendritic cells and cytokine production in CLL patients.

GM-CSF as Adjuvant Therapy of Melanoma [Completed]
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV).

Randomized Phase III Trial of Leukine® Vs Neupogen® in Patients Receiving Cisplatin & Gemcitabine for Urothelial Cancer [Terminated]
The main objective of this study is to compare the effectiveness of Leukine & Neupogen to decrease the incidence of grade 3 & 4 neutropenia in the treatment of patients receiving cisplatin & gemcitabine for urothelial (bladder) cancer.

All patients will receive chemotherapy with cisplatin plus gemcitabine in six 21-day cycles. Patients will also receive either Leukine (Arm A) or Neupogen (Arm B).

Patient Population: 100 patients will be enrolled (n=100) in this study. Patients cannot have undergone previous chemotherapy. Approximately 50 patients will be enrolled into each treatment arm.

Test Product, Dose, Mode of Administration: All patients will receive chemotherapy treatment with cisplatin (70 mg/kg) on Day 1 and gemcitabine (1000 mg/m2) on Days 1, 8, & 15 of each 21-day cycle. Patients will be randomized to receive either Leukine (250 µg/m2) or Neupogen (5 µg/kg) injected under the skin on Days 2-6, 9-13, & 16-20 of each cycle.

Duration of Treatment: Patients will receive a maximum of six 21-day cycles of treatment. The overall trial, including follow-up, is expected to be 3 years in duration.

Open-Label Trial of LEUKINE® in Active Crohn's Disease [Completed]
The purpose of this study is to establish a safety profile sargramostim administered in 8 week cycles to adult patients with active Crohn’s disease.

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