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Treatment Optimization of Newly Diagnosed Ph/BCR-ABL Positive Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase With Nilotinib vs. Nilotinib Plus Interferon Alpha Induction and Nilotinib or Interferon Alpha Maintenance Therapy

Phase 3
18 Years
Open (Enrolling)
Chronic Myeloid Leukemia

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Trial Information

Treatment Optimization of Newly Diagnosed Ph/BCR-ABL Positive Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase With Nilotinib vs. Nilotinib Plus Interferon Alpha Induction and Nilotinib or Interferon Alpha Maintenance Therapy



- Evaluation of the major molecular response (MMR) rate at 18 months of nilotinib
compared to nilotinib+pegylated Interferon alpha (IFN) in adult patients with newly
diagnosed Ph/BCR-ABL CML in chronic phase.

- Evaluation of the feasibility to discontinue drug therapy in stable deep molecular
response (MR4) after nilotinib versus IFN maintenance therapy.


- Evaluation of the efficacy and tolerability of IFN added to nilotinib 2x300 mg/day.

- Evaluation of the efficacy and tolerability of a maintenance therapy with nilotinib
versus IFN after stable MMR after at least 24 months of nilotinib therapy.

Inclusion Criteria:

- Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph
chromosome [t(9;22)(q34;q11)]

- Ph negative cases or patients with variant translocations who are BCR-ABL positive in
multiplex PCR (Cross, et al 1994) are eligible as well

- ECOG performance status of < 2

- Pretreatment with hydroxyurea for 6 months and imatinib or nilotinib for a duration
of up to 6 weeks is permitted

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

- Normal serum levels ≥ LLN (lower limit of normal) of potassium, magnesium, total
calcium corrected for serum albumin, or corrected to within normal limits with

- ASAT and ALAT ≤ 2.5 x ULN (upper limit of normal) or ≤ 5.0 x ULN if considered due to

- Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukemia

- Total bilirubin ≤ 1.5 x ULN, except known Mb. Gilbert

- Serum lipase and amylase ≤ 1.5 x ULN

- Serum creatinine ≤ 2 x ULN

- Written informed consent prior to any study procedures being performed

Exclusion Criteria:

- Known impaired cardiac function, including any of the following:

- Left ventricular ejection fraction (LVEF) < 45%

- Congenital long QT syndrome

- History of or presence of clinically significant ventricular or atrial

- Clinically significant resting bradycardia (< 50 beats per minute)

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

- Myocardial infarction within 12 months prior to starting therapy

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

- History of acute (i.e., within 1 year of starting study medication) or chronic

- Acute or chronic viral hepatitis with moderate or severe hepatic impairment
(Child-Pugh scores > 6), even if controlled

- Other 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

- Concomitant medications known to be strong inducers or inhibitors of the CYP450
isoenzyme CYP3A4

- 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

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

- Active autoimmune disorder, including autoimmune hepatitis

- Known serious hypersensitivity reactions to peginterferon alfa-2b or interferon
alfa-2b or drug excipients

- Known serious hypersensitivity reactions to nilotinib

- 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:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

MMR rate at 18 months of nilotinib monotherapy versus nilotinib+pegylated interferon alpha

Outcome Description:

rate of MMR 18 months after randomization for each study treatment

Outcome Time Frame:

at least 18 months after start of study treatment

Safety Issue:


Principal Investigator

Andreas Hochhaus, Prof. MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jena University Hospital


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

August 2012

Completion Date:

December 2020

Related Keywords:

  • Chronic Myeloid Leukemia
  • CML
  • Tasigna
  • Nilotinib
  • Interferon
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive