Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible (PAZOPANIB-AML)
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring (other than AML M3)
Eligibility Criteria
Inclusion Criteria:
- Subjects must provide written informed consent prior to performance of study-specific procedures or assessments which are not routinely performed for diagnosis or monitoring of acute myeloid leukemia (AML), and the subjects must be willing to comply with treatment and to follow up assessments and procedures
- Histologically or cytologically confirmed diagnosis of AML relapsed after or refractory to at least one induction regimen, or patients with AML at initial diagnosis who are not eligible for allogeneic transplant or intensive induction chemotherapy, except for AML M3 (acute promyelocytic leukemia)
- Age at least 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤3
- Measurable disease burden (blasts in BM and/or PB, extramedullary blasts [chloroma])
- Able to swallow and retain oral medication
- A life expectancy of at least 4 weeks
- Adequate contraception methods
- Adequate organ function as defined in the study protocol
Exclusion Criteria:
- Patients with a valid option for intensive chemotherapy and/or stem cell transplantation (Patients after allogeneic stem cell transplant must be off immunosuppressive agents for at least 2 weeks prior to study entry and Graft-versus host disease must have resolved to Grade ≤2)
- History of cancer that according to the Investigator might confound the assessment of the endpoints of the study
- Uncontrolled peptic ulcer disease or clinically significant gastrointestinal abnormalities which interfere with oral dosing or any unstable or serious concurrent condition (e.g., active uncontrolled infection)
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥90 mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study
- Prolongation of corrected QT interval (QTc) >480 milliseconds
- History of any one of more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- History of cerebrovascular infarction or bleeding, pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents for at least 6 weeks are eligible
- Evidence of serious active bleeding or bleeding diathesis (except for bleeding or petechiae due to AML-related thrombocytopenia which will be treated using platelet transfusions). Also, patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels will be excluded from the study due to excess risk of bleeding.
- Prior major surgery or trauma within 28 days prior to first dose of study drug
- Treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug (for bevacizumab 60 days).
- Concurrent cytoreductive chemotherapy (hydroxyurea must be discontinued at least one day before start of study medication)
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to pazopanib
- Patients with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
- Pregnant or lactating and actively breastfeeding patients
Patients taking any of the following prohibited medication:
- clarithromycin, telithromycin, troleandomycin (antibiotics)
- ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir (HIV protease inhibitors)
- itraconazole, ketoconazole, voriconazole, fluconazole (antifungals)
- nefazodone (antidepressant)
Sites / Locations
- Unviersity Hospital of Münster (UKM)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib
Arm Description
Pazopanib treatment
Outcomes
Primary Outcome Measures
Cumulative response rate (CR, CRp, CRi, PR) within up to one year of pazopanib treatment
Reduction of BM microvessel density on day 28
Secondary Outcome Measures
Safety and Tolerability (Rate of adverse events)
Rate of adverse events
Cumulative incidence and degree of inhibition of target receptor phosphorylation (PDGFR, VEGFR, and c-KIT) and correlation with clinical response
Reduction of BM microvessel density on day 14
Relapse-free survival in relationship to historical control patients, Overall survival in relationship to historical control patients, Duration of response
Full Information
NCT ID
NCT01361334
First Posted
May 17, 2011
Last Updated
April 6, 2021
Sponsor
University Hospital Muenster
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01361334
Brief Title
Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible
Acronym
PAZOPANIB-AML
Official Title
Phase II Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Muenster
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Long term disease-free survival (DFS) of patients with acute myeloid leukemia (AML) is still poor. Recently, so-called "targeted therapy" for cancer has been introduced to the treatment of patients with AML. This phase II clinical trial will explore the efficacy, safety, and pharmacodynamics of the tyrosine kinase inhibitor pazopanib in patients with relapsed or refractory AML or patients with AML who are not eligible for intensive treatment. Biomarker studies will be included to study whether the targets are indeed inhibited and whether this leads to decreased BM angiogenesis. Toxicity assessments will be included, and the antileukemic effectiveness will be studied.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
(other than AML M3)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib
Arm Type
Experimental
Arm Description
Pazopanib treatment
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
Votrient(R)
Intervention Description
800 mg QD p.o.
Primary Outcome Measure Information:
Title
Cumulative response rate (CR, CRp, CRi, PR) within up to one year of pazopanib treatment
Time Frame
12 months
Title
Reduction of BM microvessel density on day 28
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Safety and Tolerability (Rate of adverse events)
Description
Rate of adverse events
Time Frame
12 months
Title
Cumulative incidence and degree of inhibition of target receptor phosphorylation (PDGFR, VEGFR, and c-KIT) and correlation with clinical response
Time Frame
12 months
Title
Reduction of BM microvessel density on day 14
Time Frame
14 days
Title
Relapse-free survival in relationship to historical control patients, Overall survival in relationship to historical control patients, Duration of response
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must provide written informed consent prior to performance of study-specific procedures or assessments which are not routinely performed for diagnosis or monitoring of acute myeloid leukemia (AML), and the subjects must be willing to comply with treatment and to follow up assessments and procedures
Histologically or cytologically confirmed diagnosis of AML relapsed after or refractory to at least one induction regimen, or patients with AML at initial diagnosis who are not eligible for allogeneic transplant or intensive induction chemotherapy, except for AML M3 (acute promyelocytic leukemia)
Age at least 18 years
Eastern Cooperative Oncology Group (ECOG) performance status of ≤3
Measurable disease burden (blasts in BM and/or PB, extramedullary blasts [chloroma])
Able to swallow and retain oral medication
A life expectancy of at least 4 weeks
Adequate contraception methods
Adequate organ function as defined in the study protocol
Exclusion Criteria:
Patients with a valid option for intensive chemotherapy and/or stem cell transplantation (Patients after allogeneic stem cell transplant must be off immunosuppressive agents for at least 2 weeks prior to study entry and Graft-versus host disease must have resolved to Grade ≤2)
History of cancer that according to the Investigator might confound the assessment of the endpoints of the study
Uncontrolled peptic ulcer disease or clinically significant gastrointestinal abnormalities which interfere with oral dosing or any unstable or serious concurrent condition (e.g., active uncontrolled infection)
Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥90 mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study
Prolongation of corrected QT interval (QTc) >480 milliseconds
History of any one of more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
History of cerebrovascular infarction or bleeding, pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents for at least 6 weeks are eligible
Evidence of serious active bleeding or bleeding diathesis (except for bleeding or petechiae due to AML-related thrombocytopenia which will be treated using platelet transfusions). Also, patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels will be excluded from the study due to excess risk of bleeding.
Prior major surgery or trauma within 28 days prior to first dose of study drug
Treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug (for bevacizumab 60 days).
Concurrent cytoreductive chemotherapy (hydroxyurea must be discontinued at least one day before start of study medication)
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to pazopanib
Patients with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
Pregnant or lactating and actively breastfeeding patients
Patients taking any of the following prohibited medication:
clarithromycin, telithromycin, troleandomycin (antibiotics)
ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir (HIV protease inhibitors)
itraconazole, ketoconazole, voriconazole, fluconazole (antifungals)
nefazodone (antidepressant)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Torsten Kessler, MD
Organizational Affiliation
University of Münster, Department of Medicine A, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Unviersity Hospital of Münster (UKM)
City
Münster
ZIP/Postal Code
48149
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
30903275
Citation
Kessler T, Koschmieder S, Schliemann C, Crysandt M, Mikesch JH, von Stillfried S, Stelljes M, Pohlen M, Lenz G, Kirsch A, Vehring K, Wardelmann E, Hartmann W, Bormann E, Gerss J, Brummendorf TH, Muller-Tidow C, Berdel WE. Phase II clinical trial of pazopanib in patients with acute myeloid leukemia (AML), relapsed or refractory or at initial diagnosis without an intensive treatment option (PazoAML). Ann Hematol. 2019 Jun;98(6):1393-1401. doi: 10.1007/s00277-019-03651-9. Epub 2019 Mar 21.
Results Reference
derived
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Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible
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