Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005243

Trial Description

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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

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Trial Acronym

TIGER

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Advances in Chronic Myeloid Leukemia (CML) therapy led to an expected survival prolongation
of > 20 years after diagnosis. So far, discontinuation of tyrosine kinase inhibitors led to
recurrence of disease in the majority of patients. The trial aims to improve treatment
strategies in CML by improving induction therapy and deescalating maintenance therapy using
low dose IFN as inducer of immunosurveillance. The trial will provide important data on the
duration of active therapy in CML patients. Considering the rapidly increasing prevalence of
CML this is of individual but also socioeconomic importance.

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Brief Summary in Scientific Language

Objectives

Primary:

- 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.

Secondary:

- 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.

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Organizational Data

  •   DRKS00005243
  •   2013/10/18
  •   2012/07/09
  •   yes
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Secondary IDs

  •   2010-024262-22 
  •   NCT01657604  (ClinicalTrials.gov)
  •   CML V  (University of Jena)
  •   2010-024262-22 
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Health Condition or Problem studied

  •   Chronic Myeloid Leukemia
  •   C92.1 -  Chronic myeloid leukaemia
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Interventions/Observational Groups

  •   Drug: Peginterferon α2b
  •   Drug: Nilotinib
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Diagnostic
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- 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 MMR 18 months after randomization for each study treatment
- rate of continuous MMR after discontinuation of nilotinib versus pegylated interferon alpha; time frame: at least 12 months after stopping all therapy; rate of patients with molecular relapse (loss of MMR) 12 months after discontinuation of any treatment for CML

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Secondary Outcome

- rate of CCyR and MMR; time frame: at 12, 18 and 24 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); this time to-event endpoints give an impression of the velocity of drug response and of the time until a certain remission should be waited for
- 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)
- Progression-Free Survival (PFS); time frame: at 12, 24 and 60 months after start of treatment
- Rate of patients off treatment for at least 6 months; time frame: at 60 months after start of treatment; all patients and comparison of treatment arms
- 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); the time of risk is the time while receiving the therapy plus 28 days thereafter
- patients compliance to nilotinib based therapies; time frame: until stop of study treatment (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)
- pharmacoeconomics of the treatment strategies; time frame: after end of study (expected in December 2020) (up to 8 years)
- Overall Survival (OS); time frame: at 12, 24 and 60 months after start of treatment

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2012/08/31
  •   652
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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

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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

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Addresses

  • start of 1:1-Block address primary-sponsor
    • University of Jena
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    • Jena University Hospital
    • Andreas Hochhaus, Prof. MD 
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    • Andreas Hochhaus, Prof. MD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   6
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.