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)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by University Hospital Muenster.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT01361334
First received: May 17, 2011
Last updated: May 25, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • Cumulative response rate (CR, CRp, CRi, PR) within up to one year of pazopanib treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Reduction of BM microvessel density on day 28 [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Tolerability (Rate of adverse events) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Rate of adverse events

  • Cumulative incidence and degree of inhibition of target receptor phosphorylation (PDGFR, VEGFR, and c-KIT) and correlation with clinical response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Reduction of BM microvessel density on day 14 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Relapse-free survival in relationship to historical control patients, Overall survival in relationship to historical control patients, Duration of response [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: June 2011
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib
Pazopanib treatment
Drug: Pazopanib
800 mg QD p.o.
Other Name: Votrient(R)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01361334

Contacts
Contact: Steffen Koschmieder, MD +49-251-8352671 koschmie@uni-muenster.de
Contact: Torsten Kessler, MD +49-251-8347602 torsten.kessler@ukmuenster.de

Locations
Germany
Unviersity Hospital of Münster (UKM) Not yet recruiting
Münster, Germany, 48149
Sponsors and Collaborators
University Hospital Muenster
GlaxoSmithKline
Investigators
Principal Investigator: Steffen Koschmieder, MD University of Münster, Department of Medicine A, Germany
  More Information

No publications provided

Responsible Party: PD Dr. med. Steffen Koschmieder, University of Münster, Department of Medicine A (Hematology, Oncology, Pneumology), Germany
ClinicalTrials.gov Identifier: NCT01361334     History of Changes
Other Study ID Numbers: UKM09_0018_PAZOPANIB_AML 2011, 2010-024526-37
Study First Received: May 17, 2011
Last Updated: May 25, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:
(other than AML M3)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 27, 2014