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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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