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
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Cumulative response rate (CR, CRp, CRi, PR) within up to one year of pazopanib treatment
Secondary Outcome
Safety and Tolerability (Rate of adverse events)
Condition
Acute Myeloid Leukemia
Intervention
Pazopanib
Study Arms / Comparison Groups
Pazopanib
Description: Pazopanib treatment
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
June 2011
Completion Date
March 2016
Primary Completion Date
March 2016
Eligibility Criteria
Inclusion Criteria:
1. 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
2. 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)
3. Age at least 18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤3
5. Measurable disease burden (blasts in BM and/or PB, extramedullary blasts [chloroma])
6. Able to swallow and retain oral medication
7. A life expectancy of at least 4 weeks
8. Adequate contraception methods
9. Adequate organ function as defined in the study protocol
Exclusion Criteria:
1. 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)
2. History of cancer that according to the Investigator might confound the assessment of
the endpoints of the study
3. 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)
4. 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
5. Prolongation of corrected QT interval (QTc) >480 milliseconds
6. 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)
7. 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
8. 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.
9. Prior major surgery or trauma within 28 days prior to first dose of study drug
10. 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).
11. Concurrent cytoreductive chemotherapy (hydroxyurea must be discontinued at least one
day before start of study medication)
12. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to pazopanib
13. Patients with psychological, familial, sociological, or geographical conditions that
do not permit compliance with the protocol
14. Pregnant or lactating and actively breastfeeding patients
15. 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Torsten Kessler, MD, ,
Location Countries
Germany
Location Countries
Germany
Administrative Informations
NCT ID
NCT01361334
Organization ID
UKM09_0018_PAZOPANIB_AML 2011
Secondary IDs
2010-024526-37
Responsible Party
Sponsor
Study Sponsor
University Hospital Muenster
Collaborators
Novartis
Study Sponsor
Torsten Kessler, MD, Principal Investigator, University of Münster, Department of Medicine A, Germany
Verification Date
May 2016