AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin

April 7, 2014 updated by: M.D. Anderson Cancer Center

Phase I/II Study of AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin

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:

  1. To determine the clinical safety and tolerability of AMG 531 administered following chemotherapy in patients with advanced malignancy
  2. To determine an optimal biologic dose (OBD) of AMG 531 administered in patients receiving chemotherapy known to cause severe thrombocytopenia
  3. To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy

Secondary Objective:

1. To evaluate limited pharmacokinetics of AMG 531 administered by S.C. route post-chemotherapy

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with a diagnosis of solid tumors who are at high risk for chemotherapy-induced severe thrombocytopenia related to the following regimens: (a) Carboplatin (AUC=11); (b) AI regimen (adriamycin 75-90mg/m2, Ifosfamide 10gm/m2); (c) High dose Ifosfamide (14gm/m2)
  2. Age >/= 18 years.
  3. Adequate hematologic (Absolute neutrophil count (ANC) >/= 1500/mm^3, platelet count >/= 100 x 10^9/L and Hgb >/= 8 gm/dL), renal (serum creatinine </= 2.0 mg/dL), and hepatic functions (total bilirubin </= 2 times, aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) </= 3 times the upper limit of the respective normal range).
  4. Karnofsky Performance Status >/= 80
  5. Signed informed consent form
  6. Patients with childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) must have a negative pregnancy test and use adequate birth control. [i.e. oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, use of an intrauterine device (IUD), or abstinence].

Exclusion Criteria:

  1. Patients with rapidly progressive disease (such as patients with rapidly accumulating ascites or pleural effusion).
  2. Patients with hematologic malignancies.
  3. Pregnant or lactating women.
  4. History of central nervous system (CNS) metastasis.
  5. Patients with significant cardiac disease (New York Hearth Association (NYHA) Class III or IV), dysrrhythmia, or recent history of MI or ischemia, transient ischemic attack or cerebrovascular accident (CVA), within the previous 6 months of study entry.
  6. Patients with a history of thromboembolic events (history of deep venous thrombosis (DVT) or pulmonary embolus).
  7. Prior chemotherapy, immunotherapy, or experimental drug (not FDA-approved drug) within 3 weeks. Patients will be eligible if day 1 of chemotherapy was initiated 3 weeks prior to study entry if the patient has recovery of blood counts and from acute toxicity of chemotherapy as described in inclusion criteria # 3.
  8. Use of nitrosourea (carmustine (BCNU), lomustine (CCNU) or mitomycin - C within 6 weeks of study entry.
  9. Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.
  10. Patients with history of prior whole pelvic radiation will be excluded unless there is no prior history of severe thrombocytopenia (i.e. platelet nadir <10,000/mm^3)
  11. Patients with history of prior high dose chemotherapy with stem cell transplant or with history of prolonged thrombocytopenia (>/= 2 weeks).
  12. History of any platelet disorders including Idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
  13. History of > 4 prior chemotherapy regimens (all platinum regimens will be counted as one regimen).
  14. Patients with significant bowel dysfunction secondary to tumor (significant abdominal pain with severe constipation/diarrhea (>/= Grade 3), significant difficulty maintaining oral nutrition).
  15. Patients with pre-existing neuropathy > Grade 2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. Adriamycin - Ifosfamide (AI) regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex
Experimental: 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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. AI regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex
Experimental: 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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. AI regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex
Experimental: 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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. AI regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex
Experimental: 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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. AI regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex
Experimental: 10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy

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 :

  1. Carboplatin [area under the concentration curve (AUC) = 11]; or
  2. AI regimen [Adriamycin 75-90 mg/m^2 intravenous (IV), Ifosfamide 10-14 gm/m^2 IV]; or
  3. High dose Ifosfamide: 14 gm/m^2.
Drug: AMG 531

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)

Other Names:
  • Romiplostim
Drug: Carboplatin
AUC=11; Cycle 1 chemotherapy alone then 3 weeks later, in Cycle 2, same dose of chemotherapy followed by AMG 531.
Other Names:
  • Paraplatin
Drug: Adriamycin
75-90 mg/m^2 IV
Other Names:
  • Rubex
  • Doxorubicin
Drug: Ifosfamide
10 gm/m^2 IV; OR, High dose ifosfamide = 14 gm/m^2.
Other Names:
  • Ifex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy
Time Frame: Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles
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
Time Frame: Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Amgen

Investigators

  • Principal Investigator: Saroj Vadhan-Raj, MD, UT MD Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

September 6, 2005

First Submitted That Met QC Criteria

September 6, 2005

First Posted (Estimate)

September 7, 2005

Study Record Updates

Last Update Posted (Estimate)

May 8, 2014

Last Update Submitted That Met QC Criteria

April 7, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-0099

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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