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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Myeloid, Chronic-Phase

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

CD34+/lin-Ph+ cells

Outcome Description:

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.

Outcome Time Frame:

6 month

Safety Issue:

No

Principal Investigator

Ester Pungolino, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Niguarda Ca' Granda Hospital

Authority:

Italy: Ethics Committee

Study ID:

PhilosoPhy34 CAMN107EIT11T

NCT ID:

NCT01856283

Start Date:

March 2013

Completion Date:

December 2018

Related Keywords:

  • Leukemia, Myeloid, Chronic-Phase
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase

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