Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Evaluation of Efficacy and Safety of Nilotinib in Combination With Chemotherapy in Elderly Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Heike Pfeifer, Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT01528085
First received: February 3, 2012
Last updated: September 29, 2015
Last verified: September 2015
  Purpose
The goal of this trial is to evaluate the efficacy and the tolerance of the combination of nilotinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of nilotinib as concomitant therapy during induction, consolidation and maintenance. The patients will be prospectively monitored for minimal residual disease and bcr-abl tyrosine kinase domain mutations.

Condition Intervention Phase
Philadelphia Chromsome Positive Acute Lymphoblastic Leukemia
Drug: Nilotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase II Study to Evaluate the Efficacy and Safety of Induction and Consolidation Therapy With Nilotinib in Combination With Chemotherapy in Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospital:

Primary Outcome Measures:
  • Evaluation of efficacy of a nilotinib-based induction and consolidation therapy [ Time Frame: after 12 months ] [ Designated as safety issue: No ]
    rate of patients without event


Secondary Outcome Measures:
  • complete haematological remission [ Time Frame: after induction treatment (week 5) ] [ Designated as safety issue: No ]
    The rate of complete haematological remission after induction treatment

  • major molecular response in bone marrow [ Designated as safety issue: No ]
    major molecular response defined by a BCR-ABL/ABL < 0.1% in bone marrow

  • complete molecular response [ Designated as safety issue: No ]
    complete molecular response defined by a BCR-ABL/ABL < 0.001% in bone marrow

  • undetectable BCR-ABL level [ Designated as safety issue: No ]
    The proportion of patients with confirmed undetectable BCR-ABL level with a test sensitivity of at least 4.5 log.

  • Event free survival [ Designated as safety issue: No ]
  • Relapse free survival [ Designated as safety issue: No ]
  • Progression free survival [ Designated as safety issue: No ]
  • T315I or p-loop Mutations [ Designated as safety issue: No ]
    Detection of a T315I or p-loop BCR-ABL TK domain mutation

  • molecular relapse or progression [ Designated as safety issue: No ]
    The proportion of patients with molecular relapse or progression

  • Overall survival [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]
    Tolerability as determined by descriptive assessment of adverse events and discontinuation due to treatment-related SAEs

  • Death during induction [ Time Frame: End of induction (week 5) ] [ Designated as safety issue: No ]
    (all patients who started treatment)

  • Death in complete remission [ Designated as safety issue: No ]

Enrollment: 79
Study Start Date: January 2012
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Nilotinib
    Nilotinib, p.o Chemotherapy (Dexamethasone, Methotroxate, Cyclophosphamide (optional), Vincristine, Vindesine, Cytarabine, 6-Mercapto-Purine)
    Other Name: Tasigna
  Eligibility

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients > 55 years
  2. Philadelphia chromosome- or BCR-ABL positive acute lymphoblastic leukemia
  3. Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted)
  4. With or without documented CNS involvement
  5. WHO performance status < 2
  6. Normal serum levels > LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin; or corrected to within normal limits with supplements, prior to the first dose of study medication
  7. Signed written inform consent
  8. Molecular evaluation for BCR-ABL performed
  9. Willingness of male subjects whose sexual partners are women of child-bearing potential (WOCBP), to use an effective form of contraception (pearl index < 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).

Exclusion Criteria:

  1. Patient previously treated with tyrosine kinase inhibitors
  2. Known impaired cardiac function, including any of the following:

    • LVEF < 45%
    • Complete left bundle branch block
    • Right bundle branch block plus left anterior hemiblock, bifascicular block
    • Use of a ventricular-paced pacemaker
    • Congenital long QT syndrome
    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib
    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
  3. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  4. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
  5. Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
  6. Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
  7. Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
  8. Concurrent severe diseases which exclude the administration of therapy
  9. Past history of acute or chronic pancreatits
  10. Patients unwilling or unable to comply with the protocol.e branch block; Right bundle branch block plus left anterior hemiblock, bifascicular block; Use of a ventricular-paced pacemaker; congenital long QT syndrome

    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib
    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)

      • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
      • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
      • Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
      • Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
      • Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
      • Concurrent severe diseases which exclude the administration of therapy
      • Past history of acute or chronic pancreatits
      • Patients unwilling or unable to comply with the protocol.
  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: NCT01528085

  Show 69 Study Locations
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
Investigators
Principal Investigator: Heike Pfeifer, Dr.med. Johann Wolfgang Goethe University Hospital
  More Information

Responsible Party: Heike Pfeifer, Dr.med., Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier: NCT01528085     History of Changes
Other Study ID Numbers: EWALL-PH-02  2010-022855-46 
Study First Received: February 3, 2012
Last Updated: September 29, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Johann Wolfgang Goethe University Hospital:
Philadelphia chromsome
BCR-ABL
ALL
acute lymphoblastic leukemia
Nilotinib
Tasigna

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes

ClinicalTrials.gov processed this record on December 02, 2016