Safety Study Evaluating Intravenous Infusions of Tigecycline to Treat Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tigecycline
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML
Eligibility Criteria
Inclusion Criteria:
- Age >18 years
- Diagnosis of relapsed or refractory AML for which all potentially curative or standard salvage therapy options have been exhausted; OR AML without prior treatment who are not eligible for induction chemotherapy as defined as age > or equal to 80 or age > 70 with poor risk cytogenetics (3 or more abnormalities, -5/del(5q), 3q abnormalities, or -7) or stable co-morbidities that would preclude induction chemotherapy such as LVEF less than 40% and/or DlCO less than 60% expected
- ECOG 0-2 performance status
- Biochemical values within the following range
- Serum creatinine <2x upper limit of normal
- Total bilirubin <1.5x upper limit of normal
- AST and ALT <2x upper limit of normal
- Recovery from non-hematologic toxicity from prior chemotherapy
- Able and willing to provide informed consent
Exclusion Criteria:
- Allergy to tetracycline or minocycline
- Uncontrolled intercurrent illness such as uncontrolled diabetes or active uncontrolled infection
- Active systemic bacterial, fungal, or viral infection
- Concomitant use of linezolid or chloramphenicol that are known to inhibit mitochondrial protein synthesis
- Pregnant or breast feeding
- Known active CNS involvement with AML
- Neurologic symptoms related to uncontrolled illnesses or unexplained causes
- Psychiatric illness that would limit compliance with study
- Receiving systemic chemotherapy other than hydroxyurea to control circulating blast counts. Concomitant hydroxyurea is permitted, but only in the first cycle of therapy
- Prior therapy with tigecycline as an anti-cancer therapy or any use of the drug in the last month
- Use of other investigational anti-leukemic therapy within 14 days of registration
Sites / Locations
- University of California, Los Angeles
- The University of Kansas Medical Center
- Princess Margaret Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tigecycline
Arm Description
Outcomes
Primary Outcome Measures
Toxicity evaluated according to CTCAE version 4.03
Secondary Outcome Measures
Response rate assessment of tigecycline through laboratory assessments
Bone marrow assessment, absolute neutrophil count, platelet counts
Full Information
NCT ID
NCT01332786
First Posted
March 31, 2011
Last Updated
April 14, 2015
Sponsor
University Health Network, Toronto
Collaborators
University of Kansas, Memorial Sloan Kettering Cancer Center, University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT01332786
Brief Title
Safety Study Evaluating Intravenous Infusions of Tigecycline to Treat Acute Myeloid Leukemia
Official Title
Phase 1 Study Evaluating the Tolerance and Biologic Activity of Intravenous Infusions of Tigecycline in Patients With Relapsed or Refractory AML
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
University of Kansas, Memorial Sloan Kettering Cancer Center, University of California, Los Angeles
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether tigecycline is safe and which dosage is most effective in the treatment of patients with acute myeloid leukemia.
Detailed Description
Relapsed and refractory hematologic malignancies have poor responses to standard therapy and are associated with a poor prognosis. For example, relapsed acute myeloid leukemia (AML) is a highly aggressive and resistant disease, particularly when associated with first complete response (CR) duration of less than 12 months. Thus, there is an urgent need for new agents in relapsed and refractory hematologic malignancies such as acute leukemia. In elderly patients, where the tolerance of aggressive induction therapy is often poor and curative options such as bone marrow transplantation HSCT are not available, the need for effective non-aggressive drug regimens for AML is even greater.
Tigecycline is a glycylcycline derivative of tetracycline. Tigecycline is currently indicated for the treatment of complicated skin and skin structure infections, and complicated intra-abdominal infections. This clinical trial is a Phase I dose escalation study of tigecycline in patients with relapsed or refractory AML or those with newly diagnosed disease not eligible for induction chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tigecycline
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tigecycline
Other Intervention Name(s)
Tygacil
Intervention Description
Dosage Form: one-hour intravenous infusion Dosage levels, frequency, duration: (3-week cycles)
Level 1: 50 mg daily x 10 doses; 1 week rest
Level 2: 100 mg daily x 10 doses; 1 week rest
Level 3: 150 mg daily x 10 doses; 1 week rest
Level 4: 200 mg daily x 10 doses 1 week rest
Level 5: 250 mg daily x 10 doses; 1 week rest
Level 6: 300 mg daily x 10 doses; 1 week rest
Level 7: 350 mg daily x 10 doses; 1 week rest
Primary Outcome Measure Information:
Title
Toxicity evaluated according to CTCAE version 4.03
Time Frame
Reviewed at each visit and assessed at the end of each 3-week cycle
Secondary Outcome Measure Information:
Title
Response rate assessment of tigecycline through laboratory assessments
Description
Bone marrow assessment, absolute neutrophil count, platelet counts
Time Frame
Assessed at the end of each 3-week cycle for the study duration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >18 years
Diagnosis of relapsed or refractory AML for which all potentially curative or standard salvage therapy options have been exhausted; OR AML without prior treatment who are not eligible for induction chemotherapy as defined as age > or equal to 80 or age > 70 with poor risk cytogenetics (3 or more abnormalities, -5/del(5q), 3q abnormalities, or -7) or stable co-morbidities that would preclude induction chemotherapy such as LVEF less than 40% and/or DlCO less than 60% expected
ECOG 0-2 performance status
Biochemical values within the following range
Serum creatinine <2x upper limit of normal
Total bilirubin <1.5x upper limit of normal
AST and ALT <2x upper limit of normal
Recovery from non-hematologic toxicity from prior chemotherapy
Able and willing to provide informed consent
Exclusion Criteria:
Allergy to tetracycline or minocycline
Uncontrolled intercurrent illness such as uncontrolled diabetes or active uncontrolled infection
Active systemic bacterial, fungal, or viral infection
Concomitant use of linezolid or chloramphenicol that are known to inhibit mitochondrial protein synthesis
Pregnant or breast feeding
Known active CNS involvement with AML
Neurologic symptoms related to uncontrolled illnesses or unexplained causes
Psychiatric illness that would limit compliance with study
Receiving systemic chemotherapy other than hydroxyurea to control circulating blast counts. Concomitant hydroxyurea is permitted, but only in the first cycle of therapy
Prior therapy with tigecycline as an anti-cancer therapy or any use of the drug in the last month
Use of other investigational anti-leukemic therapy within 14 days of registration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron Schimmer, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Safety Study Evaluating Intravenous Infusions of Tigecycline to Treat Acute Myeloid Leukemia
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