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 three 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 Progentior 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 cell counts 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 ≤ two (see
CLINICAL EXPERIENCE). Hematologic response to LEUKINE can be detected by complete blood count (CBC) with differential performed twice per week.
CLINICAL EXPERIENCE
Acute Myelogenous Leukemia
The safety and efficacy of LEUKINE in patients with AML who are younger than 55 years of age have not been determined. Based on Phase II data suggesting the best therapeutic effects could be achieved in patients at highest risk for severe infections and mortality while neutropenic, the Phase III clinical trial was conducted in older patients. The safety and efficacy of LEUKINE in the treatment of AML were evaluated in a multi-center, randomized, double-blind placebo-controlled trial of 99 newly diagnosed adult patients, 55–70 years of age, receiving induction with or without consolidation.6 A combination of standard doses of daunorubicin (days 1–3) and ara-C (days 1–7) was administered during induction and high dose ara-C was administered days 1–6 as a single course of consolidation, if given. Bone marrow evaluation was performed on day 10 following induction chemotherapy. If hypoplasia with <5% blasts was not achieved, patients immediately received a second cycle of induction chemotherapy. If the bone marrow was hypoplastic with <5% blasts on day 10 or four days following the second cycle of induction chemotherapy, LEUKINE (250 mcg/m2/day) or placebo was given IV over four hours each day, starting four days after the completion of chemotherapy. Study drug was continued until an ANC ≥1500/mm3 for three consecutive days was attained or a maximum of 42 days. LEUKINE or placebo was also administered after the single course of consolidation chemotherapy if delivered (ara-C 3–6 weeks after induction following neutrophil recovery). Study drug was discontinued immediately if leukemic regrowth occurred.
LEUKINE significantly shortened the median duration of ANC <500/mm3 by 4 days and <1000/mm3 by 7 days following induction (see
Table 1). 75% of patients receiving LEUKINE achieved ANC >500/mm3 by day 16, compared to day 25 for patients receiving placebo. The proportion of patients receiving one cycle (70%) or two cycles (30%) of induction was similar in both treatment groups; LEUKINE significantly shortened the median times to neutrophil recovery whether one cycle (12 versus 15 days) or two cycles (14 versus 23 days) of induction chemotherapy was administered. Median times to platelet (>20,000/mm3) and RBC transfusion independence were not significantly different between treatment groups.
Table 1
| Hematological Recovery (in Days): Induction |
| Dataset |
sargramostim
n=52Patients with missing data censored.
Median (25%, 75%) |
Placebo
n=47
Median (25%,75%) |
p-valuep=Generalized Wilcoxon
|
| ANC>500/mm3
2 patients on sargramostim and 4 patients on placebo had missing values.
|
13 (11, 16) |
17 (13, 25) |
0.009 |
| ANC>1000/mm3
2 patients on sargramostim and 3 patients on placebo had missing values.
|
14 (12, 18) |
21 (13, 34) |
0.003 |
| PLT>20,000/mm3
4 patients on placebo had missing values.
|
11 (7, 14) |
12 (9, >42) |
0.10 |
| RBC3 patients on sargramostim and 4 patients on placebo had missing values.
|
12 (9, 24) |
14 (9, 42) |
0.53 |
During the consolidation phase of treatment, LEUKINE did not shorten the median time to recovery of ANC to 500/mm3 (13 days) or 1000/mm3 (14.5 days) compared to placebo. There were no significant differences in time to platelet and RBC transfusion independence.
The incidence of severe infections and deaths associated with infections was significantly reduced in patients who received LEUKINE. During induction or consolidation, 27 of 52 patients receiving LEUKINE and 35 of 47 patients receiving placebo had at least one grade 3, 4 or 5 infection (p=0.02). Twenty-five patients receiving LEUKINE and 30 patients receiving placebo experienced severe and fatal infections during induction only. There were significantly fewer deaths from infectious causes in the LEUKINE arm (3 versus 11, p=0.02). The majority of deaths in the placebo group were associated with fungal infections with pneumonia as the primary infection.
Disease outcomes were not adversely affected by the use of LEUKINE. The proportion of patients achieving complete remission (CR) was higher in the LEUKINE group (69% as compared to 55% for the placebo group), but the difference was not significant (p=0.21). There was no significant difference in relapse rates; 12 of 36 patients who received LEUKINE and five of 26 patients who received placebo relapsed within 180 days of documented CR (p=0.26). The overall median survival was 378 days for patients receiving LEUKINE and 268 days for those on placebo (p=0.17). The study was not sized to assess the impact of LEUKINE treatment on response or survival.
Mobilization and Engraftment of PBPC
A retrospective review was conducted of data from patients with cancer undergoing collection of peripheral blood progenitor cells (PBPC) at a single transplant center. Mobilization of PBPC and myeloid reconstitution post-transplant were compared between four groups of patients (n=196) receiving LEUKINE for mobilization and a historical control group who did not receive any mobilization treatment [progenitor cells collected by leukapheresis without mobilization (n=100)]. Sequential cohorts received LEUKINE. The cohorts differed by dose (125 or 250 mcg/m2/day), route (IV over 24 hours or SC) and use of LEUKINE post-transplant. Leukaphereses were initiated for all mobilization groups after the WBC reached 10,000/mm3. Leukaphereses continued until both a minimum number of mononucleated cells (MNC) were collected (6.5 or 8.0 × 108/kg body weight) and a minimum number of phereses (5–8) were performed. Both minimum requirements varied by treatment cohort and planned conditioning regimen. If subjects failed to reach a WBC of 10,000 cells/mm3 by day five, another cytokine was substituted for LEUKINE; these subjects were all successfully leukapheresed and transplanted. The most marked mobilization and post-transplant effects were seen in patients administered the higher dose of LEUKINE (250 mcg/m2) either IV (n=63) or SC (n=41).
PBPCs from patients treated at the 250 mcg/m2/day dose had significantly higher number of granulocyte-macrophage colony-forming units (CFU-GM) than those collected without mobilization. The mean value after thawing was 11.41 × 104 CFU-GM/kg for all LEUKINE-mobilized patients, compared to 0.96 × 104/kg for the non-mobilized group. A similar difference was observed in the mean number of erythrocyte burst-forming units (BFU-E) collected (23.96 × 104/kg for patients mobilized with 250 mcg/m2 doses of LEUKINE administered SC vs. 1.63 × 104/kg for non-mobilized patients).
After transplantation, mobilized subjects had shorter times to myeloid engraftment and fewer days between transplantation and the last platelet transfusion compared to non-mobilized subjects. Neutrophil recovery (ANC >500/mm3) was more rapid in patients administered LEUKINE following PBPC transplantation with LEUKINE-mobilized cells (see
Table 2). Mobilized patients also had fewer days to the last platelet transfusion and last RBC transfusion, and a shorter duration of hospitalization than did non-mobilized subjects.
Table 2
| ANC and Platelet Recovery after PBPC Transplant |
|
Route for
Mobilization |
Post-transplant
LEUKINE |
ENGRAFTMENT
(median value in days) |
| ANC>500/mm3
|
Last platelet transfusion |
| No Mobilization |
— |
no |
29 |
28 |
| LEUKINE |
IV |
no |
21 |
24 |
| 250 mcg/m2
|
IV |
yes |
12 |
19 |
| Â |
SC |
yes |
12 |
17 |
A second retrospective review of data from patients undergoing PBPC at another single transplant center was also conducted. LEUKINE was given SC at 250 mcg/m2/day once a day (n=10) or twice a day (n=21) until completion of the phereses. Phereses were begun on day 5 of LEUKINE administration and continued until the targeted MNC count of 9 × 108/kg or CD34+ cell count of 1 × 106/kg was reached. There was no difference in CD34+ cell count in patients receiving LEUKINE once or twice a day. The median time to ANC>500/mm3 was 12 days and to platelet recovery (>25,000/mm3) was 23 days.
Survival studies comparing mobilized study patients to the nonmobilized patients and to an autologous historical bone marrow transplant group showed no differences in median survival time.
Autologous Bone Marrow Transplantation
Following a dose-ranging Phase I/II trial in patients undergoing autologous BMT for lymphoid malignancies,8, 9 three single center, randomized, placebo-controlled and double-blinded studies were conducted to evaluate the safety and efficacy of LEUKINE for promoting hematopoietic reconstitution following autologous BMT. A total of 128 patients (65 LEUKINE, 63 placebo) were enrolled in these three studies. The majority of the patients had lymphoid malignancy (87 NHL, 17 ALL), 23 patients had Hodgkin's disease, and one patient had acute myeloblastic leukemia (AML). In 72 patients with NHL or ALL, the bone marrow harvest was purged prior to storage with one of several monoclonal antibodies. No chemical agent was used for in vitro treatment of the bone marrow. Preparative regimens in the three studies included cyclophosphamide (total dose 120–150 mg/kg) and total body irradiation (total dose 1,200–1,575 rads). Other regimens used in patients with Hodgkin's disease and NHL without radiotherapy consisted of three or more of the following in combination (expressed as total dose): cytosine arabinoside (400 mg/m2) and carmustine (300 mg/m2), cyclophosphamide (140–150 mg/kg), hydroxyurea (4.5 grams/m2) and etoposide (375–450 mg/m2).
Compared to placebo, administration of LEUKINE in two studies (n=44 and 47) significantly improved the following hematologic and clinical endpoints: time to neutrophil engraftment, duration of hospitalization and infection experience or antibacterial usage. In the third study (n=37) there was a positive trend toward earlier myeloid engraftment in favor of LEUKINE. This latter study differed from the other two in having enrolled a large number of patients with Hodgkin's disease who had also received extensive radiation and chemotherapy prior to harvest of autologous bone marrow. A subgroup analysis of the data from all three studies revealed that the median time to engraftment for patients with Hodgkin's disease, regardless of treatment, was six days longer when compared to patients with NHL and ALL, but that the overall beneficial LEUKINE treatment effect was the same. In the following combined analysis of the three studies, these two subgroups (NHL and ALL vs. Hodgkin's disease) are presented separately.
Table 3
| Autologous BMT: Combined Analysis from Placebo-Controlled Clinical Trials of Responses in Patients with NHL and ALL Median Values (days) |
|
ANC
≥500/mm3
|
ANC
≥1000/mm3
|
Duration of
Hospitalization |
Duration of
Infection |
Duration of
Antibacterial Therapy |
| Note: The single AML patient was not included. |
LEUKINE
(n=54) |
18
|
24
|
25
|
1
|
21
|
Placebo
(n=50) |
24 |
32 |
31 |
4 |
25 |
Patients with Lymphoid Malignancy (Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia)
Myeloid engraftment (absolute neutrophil count [ANC]≥500 cells/mm3) in 54 patients receiving LEUKINE was observed 6 days earlier than in 50 patients treated with placebo (see
Table 3). Accelerated myeloid engraftment was associated with significant clinical benefits. The median duration of hospitalization was six days shorter for the LEUKINE group than for the placebo group. Median duration of infectious episodes (defined as fever and neutropenia; or two positive cultures of the same organism; or fever >38°C and one positive blood culture; or clinical evidence of infection) was three days less in the group treated with LEUKINE. The median duration of antibacterial administration in the post-transplantation period was four days shorter for the patients treated with LEUKINE than for placebo-treated patients. The study was unable to detect a significant difference between the treatment groups in rate of disease relapse 24 months post-transplantation. As a group, leukemic subjects receiving LEUKINE derived less benefit than NHL subjects. However, both the leukemic and NHL groups receiving LEUKINE engrafted earlier than controls.
Patients with Hodgkin's Disease
If patients with Hodgkin's disease are analyzed separately, a trend toward earlier myeloid engraftment is noted. LEUKINE-treated patients engrafted earlier (by five days) than the placebo-treated patients (p=0.189, Wilcoxon) but the number of patients was small (n=22).
Allogeneic Bone Marrow Transplantation
A multi-center, randomized, placebo-controlled, and double-blinded study was conducted to evaluate the safety and efficacy of LEUKINE for promoting hematopoietic reconstitution following allogeneic BMT. A total of 109 patients (53 LEUKINE, 56 placebo) were enrolled in the study. Twenty-three patients (11 LEUKINE, 12 placebo) were 18 years old or younger. Sixty-seven patients had myeloid malignancies (33 AML, 34 CML), 17 had lymphoid malignancies (12 ALL, 5 NHL), three patients had Hodgkin's disease, six had multiple myeloma, nine had myelodysplastic disease, and seven patients had aplastic anemia. In 22 patients at one of the seven study sites, bone marrow harvests were depleted of T cells. Preparative regimens included cyclophosphamide, busulfan, cytosine arabinoside, etoposide, methotrexate, corticosteroids, and asparaginase. Some patients also received total body, splenic, or testicular irradiation. Primary graft-versus-host disease (GVHD) prophylaxis was cyclosporine A and a corticosteroid.
Accelerated myeloid engraftment was associated with significant laboratory and clinical benefits. Compared to placebo, administration of LEUKINE significantly improved the following: time to neutrophil engraftment, duration of hospitalization, number of patients with bacteremia and overall incidence of infection (see
Table 4).
Table 4
| Allogeneic BMT: Analysis of Data from Placebo-Controlled Clinical Trial Median Values (days or number of patients) |
|
ANC ≥
500/mm3
|
ANC ≥
1000/mm3
|
Number of Patients
with Infections |
Number of Patients
with Bacteremia |
Days of
Hospitalization |
LEUKINE
(n=53) |
13
|
14
|
30
|
9p <0.05 simple chi-square test
|
25
|
Placebo
(n=56) |
17 |
19 |
42 |
19 |
26 |
Median time to myeloid engraftment (ANC ≥ 500 cells/mm3) in 53 patients receiving LEUKINE was 4 four days less than in 56 patients treated with placebo (see
Table 4). The number of patients with bacteremia and infection was significantly lower in the LEUKINE group compared to the placebo group (9/53 versus 19/56 and 30/53 versus 42/56, respectively). There were a number of secondary laboratory and clinical endpoints. Of these, only the incidence of severe (grade 3/4) mucositis was significantly improved in the LEUKINE group (4/53) compared to the placebo group (16/56) at p<0.05. LEUKINE-treated patients also had a shorter median duration of post-transplant IV antibiotic infusions, and shorter median number of days to last platelet and RBC transfusions compared to placebo patients, but none of these differences reached statistical significance.
Bone Marrow Transplantation Failure or Engraftment Delay
A historically-controlled study was conducted in patients experiencing graft failure following allogeneic or autologous BMT to determine whether LEUKINE improved survival after BMT failure.
Three categories of patients were eligible for this study:
- patients displaying a delay in engraftment (ANC ≤ 100 cells/mm3 by day 28 post-transplantation);
- patients displaying a delay in engraftment (ANC ≤ 100 cells/mm3 by day 21 post-transplantation) and who had evidence of an active infection; and
- patients who lost their marrow graft after a transient engraftment (manifested by an average of ANC ≥ 500 cells/mm3 for at least one week followed by loss of engraftment with ANC < 500 cells/mm3 for at least one week beyond day 21 post-transplantation).
A total of 140 eligible patients from 35 institutions were treated with LEUKINE and evaluated in comparison to 103 historical control patients from a single institution. One hundred sixty-three patients had lymphoid or myeloid leukemia, 24 patients had non-Hodgkin's lymphoma, 19 patients had Hodgkin's disease and 37 patients had other diseases, such as aplastic anemia, myelodysplasia or non-hematologic malignancy. The majority of patients (223 out of 243) had received prior chemotherapy with or without radiotherapy and/or immunotherapy prior to preparation for transplantation.
One hundred day survival was improved in favor of the patients treated with LEUKINE after graft failure following either autologous or allogeneic BMT. In addition, the median survival was improved by greater than two-fold. The median survival of patients treated with LEUKINE after autologous failure was 474 days versus 161 days for the historical patients. Similarly, after allogeneic failure, the median survival was 97 days with LEUKINE treatment and 35 days for the historical controls. Improvement in survival was better in patients with fewer impaired organs.
The MOF score is a simple clinical and laboratory assessment of seven major organ systems: cardiovascular, respiratory, gastrointestinal, hematologic, renal, hepatic and neurologic.10 Assessment of the MOF score is recommended as an additional method of determining the need to initiate treatment with LEUKINE in patients with graft failure or delay in engraftment following autologous or allogeneic BMT (see
Table 5).
Table 5
| Median Survival by Multiple Organ Failure (MOF) Category Median Survival (days) |
|
MOF ≤ 2 Organs |
MOF > 2 Organs |
MOF (Composite of Both Groups) |
|
Autologous BMT
|
|
|
|
| LEUKINE |
474 (n=58) |
78.5 (n=10) |
474 (n=68) |
| Historical |
165 (n=14) |
39 (n=3) |
161 (n=17) |
|
Allogeneic BMT
|
|
|
|
| LEUKINE |
174 (n=50) |
27 (n=22) |
97 (n=72) |
| Historical |
52.5(n=60) |
15.5(n=26) |
35 (n=86) |
Factors that Contribute to Survival
The probability of survival was relatively greater for patients with any one of the following characteristics: autologous BMT failure or delay in engraftment, exclusion of total body irradiation from the preparative regimen, a non-leukemic malignancy or MOF score ≤ two (zero, one or two dysfunctional organ systems). Leukemic subjects derived less benefit than other subjects.
|
NEWS HIGHLIGHTS
Published Studies Related to Leukine (Sargramostim)
Sargramostim (GM-CSF) for induction of remission in Crohn's disease. [2011.11.09]
CONCLUSIONS: Sargramostim does not appear to be more effective than placebo for induction of clinical remission or clinical improvement in patients with active Crohn's disease. However, the GRADE analysis indicates that the overall quality of the evidence for the primary (clinical remission) and secondary outcomes (clinical response) was low indicating that further research is likely to have an impact on the effect estimates.
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...
Clinical Trials Related to Leukine (Sargramostim)
Study of the Safety & Efficacy of Leukine� in the Treatment of Alzheimer's Disease [Recruiting]
A medicine that is FDA-approved for bone marrow stimulation (called Leukine) will be tested
for its ability to be tolerated by Alzheimer's disease patients and potentially to improve
their memory.
Leukine (Sargramostim) for Parkinson's Disease [Recruiting]
The purpose of this study is to determine if Leukine (sargramostim) can be safely
administered to Parkinson's disease patients for an extended period of time (56 days) and
restore immune deficits seen in Parkinson's patients compared to controls. The development
of magnetoencephalography (MEG) as a monitoring tool for PD will also be explored. At
enrollment and repeating again at two 4-week intervals, whole blood from PD patients and
controls will be obtained for analyses and the results will be used to calculate immune
response profiles as a baseline for comparison after drug treatment. Physical examinations
and motor assessments will also be performed on PD patients. After the 8-week baseline data
collection, control participation will end and drug treatment of PD patients will begin. PD
patients will be randomized, and half will receive drug and half will receive placebo.
Leukine at a dosage of 6 µg/kg or saline as placebo will be administered by subcutaneous
injection daily for 56 days (8 weeks). During drug treatment, PD patients will be monitored
every two weeks by physical examinations, motor assessments, and blood analyses. As
follow-up, four weeks after drug administration has stopped, subjects will again have
physical examinations, motor assessments, and blood analyses. MEG will be performed on PD
patients and controls at the start of drug treatment, and on PD patients at the end of the
drug treatment period and 4 weeks after drug is stopped. In addtion, at the second cohort of
8 PD subjects, we will evaluate the potential Leukine-induced motor control and mobility
improvements. Also, levels of the neurotransmitters glutamate, glutamine, serotonin,
acetylcholine, GABA, norepinephrine and epinephrine in serum/plasma will be analyzed to
correlate with changes in motor function and drug treatment.
Comparison Study of Rituximab Plus Sargramostim to Rituximab Alone for Relapsed Follicular B-cell Lymphoma, a Form of Non-Hodgkin's Lymphoma [Terminated]
The purpose of this study is to evaluate whether treatment with rituximab plus sargramostim
will be more effective than rituximab alone.
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.
Sargramostim or Hypertonic Saline Before Sentinel Lymph Node Biopsy in Treating Patients With Stage IB-II Melanoma [Recruiting]
This randomized phase III trial studies sargramostim before sentinel lymph node biopsy to
see how well it works compared to hypertonic saline before sentinel lymph node biopsy in
treating patients with melanoma. Biological therapies, such as sargramostim, may stimulate
the immune system in different ways and stop cancer cells from growing. It is not yet known
whether sargramostim is more effective than hypertonic saline in treating patients with
stage IB-II melanoma undergoing sentinel lymph node biopsy.
Reports of Suspected Leukine (Sargramostim) Side Effects
Diarrhoea (24),
Nausea (20),
Fatigue (18),
Dehydration (17),
Dyspnoea (16),
Abdominal Pain (15),
Pyrexia (15),
Adrenal Insufficiency (14),
Syncope (13),
Rash (12), more >>
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