TKI and Interferon Alpha Evaluation Initiated by the German Chronic Myeloid Leukemia Study Group - the TIGER Study

• Register: ClinicalTrials.gov
• Last refreshed on: 22 May 2023
• Main ID: NCT01657604
• Date of registration: 09/07/2012
• Prospective Registration: Yes
• Primary sponsor: University of Jena
• Public title: TKI and Interferon Alpha Evaluation Initiated by the German Chronic Myeloid Leukemia Study Group - the TIGER Study TIGER
• Scientific title: 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
• Date of first enrolment: August 24, 2012
• Target sample size: 717
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01657604
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Diagnostic. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Czech Republic, Czechia, Germany, Switzerland

Contacts

• Name: Andreas Hochhaus, Prof. MD
• Affiliation: Jena University Hospital

Key inclusion & exclusion criteria

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
supplements

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

- 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
tachyarrhythmias

- 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
pancreatitis

- 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
mandatory)

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Myeloid Leukemia

Intervention(s)

Drug: Nilotinib

Drug: Peginterferon a2b

Primary Outcome(s)

MMR rate at 18 months of nilotinib monotherapy versus nilotinib+pegylated interferon alpha [Time Frame: at least 18 months after start of study treatment]

rate of continuous MMR after discontinuation of nilotinib versus pegylated interferon alpha [Time Frame: at least 12 months after stopping all therapy]

Secondary Outcome(s)

safety and tolerability profile of nilotinib in comparison with nilotinib+pegylated interferon alpha and pegylated interferon alpha [Time Frame: time of first study treatment until 28 days after stop of study treatment (expected 36 months)]

Overall Survival (OS) [Time Frame: at 12, 24 and 60 months after start of treatment]

patients compliance to nilotinib based therapies [Time Frame: until stop of study treatment (at least 36 months)]

Progression-Free Survival (PFS) [Time Frame: at 12, 24 and 60 months after start of treatment]

pharmacoeconomics of the treatment strategies [Time Frame: after end of study (expected in December 2020) (up to 8 years)]

rate of MR4 and MR4.5 during maintenance therapy and after discontinuation [Time Frame: start of maintenance therapy (after at least 24 months of treatment) until end of study duration (at least 36 months)]

quality of life during induction therapy with ilotinib versus nilotinib+pegylated interferon alpha and during maintenance therapy with nilotinib versus pegylated interferon alpha [Time Frame: during induction therapy (until at least 24 months), during maintenance therapy (until at least 36 months)]

rate of CCyR and MMR [Time Frame: at 12, 18 and 24 months after start of treatment]

Rate of patients off treatment for at least 6 months [Time Frame: at 60 months after start of treatment]

Time to CCyR, MMR, MR4 and MR4.5 [Time Frame: date of randomization until time to endpoints or end of study duration (at least 36 months)]

Secondary ID(s)

2010-024262-22

CML V

Source(s) of Monetary Support

Please refer to primary and secondary sponsors