Clincosm LogoSign in Get a demo

Nilotinib 300 mg BID in Newly Diagnosed CP-CML Patients to Verify Disappearance of CD34+/Lin-Ph+ Cells

Sponsor
Niguarda Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01856283
Collaborator
(none)
87
Enrollment
17
Locations
1
Arm
94.1
Actual Duration (Months)
5.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicentre, single-arm study of nilotinib 300 mg BID in newly diagnosed patients with CP-CML. This study is designed to establish the disappearance of Ph+ stem cells (CD34+/lin-) in BM during nilotinib treatment.

In addition, in this study the investigators aim to perform Gene Expression Profiling (GEP) of CML enrolled patients using Affymetrix GeneChip Instruments and Software Systems, and Affymetrix GeneChip Human Genome U133 Plus 2.0 (whole human transcriptome analysis) at diagnosis and at 3 different time points during treatment with Nilotinib (after 3, 6, 12 months).

Condition or Disease Intervention/Treatment Phase
  • Drug: Nilotinib 300mg BID
 Phase 2

Detailed Description

This study is designed to establish the disappearance of Ph+ stem cells (CD34+/lin-) in BM during nilotinib treatment.

The primary efficacy endpoint is to measure the rate of CD34+/lin-Ph+ cells in the BM after 6 months of treatment. In order to obtain this result, BM blood of all enrolled patients will be stored after 6 months of treatment with nilotinib. The isolated CD34+/lin- cells will be employed for standard FISH analysis. These endpoints will be obtained at the central laboratory of Niguarda Ca' Granda Hospital, Milano, Italy.

Secondary endpoints will be reached performing:

  • the same analyzes on CD34+/lin- cells at diagnosis, at 3 and 12 months of treatment;

  • cytogenetic analysis to estimate the rate of CCyR at 3, 6 and 12 months; this analysis will be performed at each local laboratory;

  • molecular analysis to determinate the rate of MR (≤ 10%, ≤ 1%, MMR, MR4,5 IS) at 3, 6 and 12 months in the peripheral blood; the molecular analysis will be performed using the Labnet standardized laboratories in Lombardy.

Study Design

Study Type:
Interventional
Actual Enrollment :
87 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Single Arm, Phase II Study of Nilotinib 300 mg BID in Newly Diagnosed CP-CML Patients, in Order to Verify Disappearance of CD34+/Lin-Ph+ Cells From Bone Marrow During Treatment
Actual Study Start Date :
Mar 1, 2013
Actual Primary Completion Date :
Jul 1, 2020
Actual Study Completion Date :
Jan 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nilotinib

study of nilotinib 300 mg BID

Drug: Nilotinib 300mg BID
Nilotinib
Other Names:
  • Nilotinib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. CD34+/lin-Ph+ cells [6 month]

      To measure the rate of CD34+/lin-Ph+ cells in the BM after 6 months of treatment. In order to obtain this result, BM blood of all enrolled patients (see Appendix 1) will be stored after 6 months of treatment with nilotinib. The isolated CD34+/lin- cells will be employed for standard FISH analysis.

    Secondary Outcome Measures

    1. CD34+/lin- cells (composite measure) [12 month]

      Secondary endpoints will be reached performing: the same analyzes on CD34+/lin- cells at diagnosis, at 3 and 12 months of treatment; cytogenetic analysis to estimate the rate of CCyR at 3, 6 and 12 months; this analysis will be performed at each local laboratory; molecular analysis to determinate the rate of MR (≤ 10%, ≤ 1%, MMR, MR4,5 IS) at 3, 6 and 12 months in the peripheral blood; the molecular analysis will be performed using the Labnet standardized laboratories in Lombardy. The Outcome Measure indicates that the measure is a composite.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome (9;22) translocation within 3 months of diagnosis

    • Patients Ph negative or with variant translocations by standard cytogenetic analysis but Ph positive by FISH, are eligible as well

    • Age ≥ 18 years old (no upper age limit given)

    • WHO performance status ≤2

    • Normal serum levels ≥ LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements, prior to the first dose of study medication

    • AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia

    • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia

    • Total bilirubin ≤ 1.5 x ULN, except know Mb Gilbert

    • Serum lipase and amylase ≤ 1.5 x ULN

    • Serum creatinine ≤ 1.5 x ULN

    • Written informed consent signed prior to any study procedures being performed

    Exclusion Criteria:

    • Pre-treatment with HU for > 3 months and with imatinib is not permitted

    • Prior accelerated phase including clonal evolution or blast crisis

    • Contraindication to excipients in study medication

    • impaired cardiac function including any of the following:

    1. LVEF <45%

    2. Complete left bundle branch block

    3. Right bundle branch block plus left anterior hemiblock,bifascicular block

    4. Use of a ventricular-paced pacemaker

    5. Congenital long QT syndrome

    6. Clinically significant ventricular or atrial tachyarrhythmias

    7. Clinically significant resting bradycardia (<50 beats per minute)

    8. QTcF >450 msec on screening ECG.If QTcF >450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion

    9. Myocardial infarction within 12 months prior to starting nilotinib

    10. Other clinical significant heart disease (e.g. unstable angina,congestive heart failure,uncontrolled hypertension)

    • Acute (i.e. within 1 year of starting study medication) or chronic pancreatitis

    • Concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections,acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol

    • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g.ulcerative disease,uncontrolled nausea,vomiting and diarrhea,malabsorption syndrome,small bowel resection or gastric by-pass surgery)

    • Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm)

    • Concomitant medications known to be strong inducers or inhibitors of the CYP450 Isoenzyme CYP3A4:see link for complete list (http://medicine.iupui.edu/flockhart/table.htm)

    • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

    • Patients who are pregnant or breast feeding or women of reproductive potential not employing an effective method of birth control.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib.Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential.Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug

    • Treatment with any haematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) ≤1 week prior to starting study drug

    • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

    • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

    • Patients unwilling or unable to comply with the protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 A.O. Ospedale S. Antonio Gallarate Milano Italy
    2 Ospedale Desio- "Ospedale Civile" di Vimercate, Desio, Carate Brianza, Giussano, Seregno. Vimercate Milano Italy
    3 A.O di Circolo di Busto Arsizio Busto Arsizio Varese Italy
    4 Ospedali Riuniti Bergamo Bergamo Italy
    5 Spedali Civili Brescia Brescia Italy
    6 Ospedale Valduce Como Italy
    7 Istituti Ospitalieri di Cremona Cremona Italy
    8 A.O Ospedale Lecco Lecco Italy
    9 Ospedale San Raffaele Milano Italy Italy
    10 A.O Sacco Milano Italy
    11 Istituto dei Tumori Milano Italy
    12 Istituto Europeo Oncologia Milano Italy
    13 Ospedale Maggiore Policlinico Milano Italy
    14 Ospedale S. Paolo Milano Italy
    15 S. Gerardo di Monza Monza Italy
    16 Policlinico S.Matteo Pavia Pavia Italy
    17 A.O. Universitaria Fondazione Macchi Varese Italy

    Sponsors and Collaborators

    • Niguarda Hospital

    Investigators

    • Principal Investigator: Ester Pungolino, MD, Niguarda Ca' Granda Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Niguarda Hospital
    ClinicalTrials.gov Identifier:
    NCT01856283
    Other Study ID Numbers:
    • PhilosoPhy34 CAMN107EIT11T
    First Posted:
    May 17, 2013
    Last Update Posted:
    Jan 13, 2021
    Last Verified:
    Jan 1, 2021
    Additional relevant MeSH terms:
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Leukemia, Myeloid, Chronic-Phase

    Study Results

    No Results Posted as of Jan 13, 2021