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| Name | Class |
|---|---|
| Amgen | INDUSTRY |
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The goal of this clinical research study is to find the highest safe dose of AMG 531 that will decrease the risk and severity of thrombocytopenia (low platelet counts) in patients who have received chemotherapy. Researchers will also look at the safety and effectiveness of AMG 531 (Romiplostim).
Primary Objectives:
Secondary Objective:
1. To evaluate limited pharmacokinetics of AMG 531 administered by S.C. route post-chemotherapy
Platelets are cells that help make the blood clot. A decrease in platelets can cause bleeding, which may prevent or delay a patient from receiving chemotherapy. Researchers want to find out if AMG 531 can lower the risk and severity of this side effect. AMG 531 is a protein that stimulates platelet production.
If you are eligible to take part in this study, you will be assigned to 1 of 6 dosing schedules of study drug. The dose of AMG 531 that you receive will depend on when you are enrolled.
In Cycle 1, all patients will receive chemotherapy by itself. Three (3) weeks later, in Cycle 2, the same dose of chemotherapy will be given followed by AMG 531. AMG 531 will be given on one of 3 schedules. AMG 531 will be given as an injection under the skin on the day after chemotherapy and 2 days later; it will be given 5 days before and the day after chemotherapy; or it will be given 5 and 3 days before chemotherapy and on the day after chemotherapy and 2 days later. The schedule you receive will depend on when you enroll on the study. After 2 cycles of treatment, based on response of the disease and tolerance to the treatment, all participants may be able to receive up to 4 more cycles of chemotherapy followed by AMG 531. All participants will continue on the same schedule you were receiving before. The dose of AMG 531 may be increased at one time point during the study based on the response of the platelet counts.
The number of blood tests drawn (about 3 teaspoons each) will depend on your clinical condition. These samples will be taken at least 2 times a week and as often as once a day during portions of the study. You will also have blood (about 1 teaspoon) collected for the evaluation of anti-AMG 531 antibody status before treatment starts, at the end of Cycles 2 and 4, and at the end of study.
You will be taken off the study if your disease gets worse or intolerable side effects occur. At the end of the study, you will have a medical history and physical exam, including measurement of vital signs. You will also have blood (about 1 teaspoon) drawn for routine tests.
This is an investigational study. AMG 531 is not FDA approved or commercially available. At this time, it is being used for research purposes only. Up to 56 patients will take part in this study. All will be enrolled at University of Texas (UT)MD Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 mcg/kg AMG 531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 1 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
|
| 3 mcg/kg AMG 531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
|
| 10 mcg/kg AMG 531 Post Chemotherapy | Experimental | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AMG 531 | Drug | Beginning with Cycle 2, administered in one of two schedules, either on day after chemotherapy and 2 days later (study cycle) or on day -5 (pre dose) and on day after chemotherapy (post dose) or combination of pre/post days of 21-28 day treatment cycle. Combination if Optimal biological dose (OBD) not reached, additional treatment at 10 mcg/kg dose level, with AMG 531 administered on day -5 (pre dose) and on day after chemotherapy (post dose). 1, 3, or 10 mcg/kg given as injection under the skin (subcutaneous) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy | Number of participants experiencing an adverse event (AE) or serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. | Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles |
| Number of Participants With Venous Thromboembolism (VTE) Related Serious Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy | Number of participants experiencing an venous thromboembolism (VTE) related serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. VTE events reported are part or whole total number reported for study SAEs, not in addition to SAEs reported. | Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Saroj Vadhan-Raj, MD | UT MD Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| UT MD Anderson Cancer Center | View source |
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Of the 55 participants enrolled, one participant was enrolled but was a screen failure and another three withdrew without receiving any study drug thus were excluded from the trial demographics.
Recruitment Period: 08/04/05 to 04/09/12. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 mcg/kg AMG 531 Post Chemotherapy | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 1 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
| FG001 | 3 mcg/kg AMG 531 Post Chemotherapy | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
| FG002 | 10 mcg/kg AMG 531 Post Chemotherapy | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later (study cycle) of 21-28 day treatment cycle. Chemotherapy :
|
| FG003 | 10 mcg/kg Pre/Post Chemotherapy | Cycle 1, Chemotherapy (Control Cycle); Beginning Cycle 2, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy (post dose) of 21-28 day treatment cycle. Chemotherapy :
|
| FG004 | 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle. Chemotherapy :
|
| FG005 | 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle. Chemotherapy :
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by AMG 531 subcutaneously of 21-28 day treatment cycle. There were 51 participants who received at least one dose of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 1 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later |
| BG001 | 3 mcg/kg AMG 531 Post Chemotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy | Number of participants experiencing an adverse event (AE) or serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. | All participants who received treatment were evaluable for toxicity; therefore 51 participants who received at least one dose of the study drug were evaluable for toxicity. | Posted | Number | participants | Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles |
|
Adverse events reported once the participant received their first dose of study drug, AMG 531 in Cycle 2 up to 6 cycles. Cycles were 21 to 28 days. The total study period was from August 5, 2005 to May 11, 2012.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 1 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Saroj Vadhan-Raj | University of Texas MD Anderson Cancer Center | 713-792-7966 | svadhanr@mdanderson.org |
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| ID | Term |
|---|---|
| D013921 | Thrombocytopenia |
| ID | Term |
|---|---|
| D001791 | Blood Platelet Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000095542 | Cytopenia |
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| ID | Term |
|---|---|
| C488777 | romiplostim |
| D016190 | Carboplatin |
| D004317 | Doxorubicin |
| D007069 | Ifosfamide |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
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| 10 mcg/kg Pre/Post Chemotherapy | Experimental | Cycle 1, Chemotherapy (Control Cycle); Beginning Cycle 2, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy (post dose) of 21-28 day treatment cycle. Chemotherapy :
|
|
| 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Experimental | Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle. Chemotherapy :
|
|
| 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Experimental | 10 mcg/kg AMG 531 + Pre/Pre/Post/Post Chemotherapy Cycle 1, Chemotherapy alone (Control Cycle); Beginning Cycle 2, Chemotherapy followed by 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) of 21-28 day treatment cycle. Chemotherapy :
|
|
|
|
| Carboplatin | Drug | AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531. |
|
|
| Adriamycin | Drug | 75-90 mg/m^2 IV |
|
|
| Ifosfamide | Drug | 10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2. |
|
|
| Adverse Event |
|
| Screen Failure |
|
| Chemotherapy Changed |
|
Cycle 1: Chemotherapy
Cycle 2: Chemotherapy, 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later
| BG002 | 10 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later |
| BG003 | 10 mcg/kg Pre/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy |
| BG004 | 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) |
| BG005 | 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 3 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later |
| OG002 | 10 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later |
| OG003 | 10 mcg/kg Pre/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy |
| OG004 | 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) |
| OG005 | 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) |
|
|
| Primary | Number of Participants With Venous Thromboembolism (VTE) Related Serious Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy | Number of participants experiencing an venous thromboembolism (VTE) related serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. VTE events reported are part or whole total number reported for study SAEs, not in addition to SAEs reported. | All participants who received treatment were evaluable for toxicity; therefore 51 participants who received at least one dose of the study drug were evaluable for toxicity. | Posted | Number | participants | Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | 3 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 3 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later | 0 | 6 | 0 | 6 |
| EG002 | 10 mcg/kg AMG 531 Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on day after chemotherapy and 2 days later | 1 | 6 | 1 | 6 |
| EG003 | 10 mcg/kg Pre/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 subcutaneously on Day -5 (pre dose) and on day after chemotherapy | 0 | 11 | 4 | 11 |
| EG004 | 5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 5 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) | 2 | 10 | 5 | 10 |
| EG005 | 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy | Cycle 1: Chemotherapy Cycle 2: Chemotherapy, 10 mcg/kg AMG 531 for 2 doses on Days -5 and -3 (pre doses) and on day after chemotherapy and 2 days later (post doses) | 0 | 12 | 8 | 12 |
| Deep Vein Thrombosis | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flu-Like Symptoms | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Skin/rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cramp | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, Bone | General disorders | CTCAE (3.0) | Systematic Assessment | Also includes back pain, neck pain or extremity pain |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombocytosis (>/= 1,000,000/mm^3) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D009279 |
| Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Deep Vein Thrombosis (DVT) |
|
| Total VTE Related SAEs |
|