Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients

Completed · Phase 2

Conditions studied: Chronic Myelogenous Leukemia

In brief

The main purpose of the study was to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients who responded optimally on this treatment

Key facts

Study ID

NCT01784068

Run by

Novartis Pharmaceuticals

People needed

215

Starts

2013-03-19

Expected to finish

2025-01-23

Last updated by the study team

2025-09-10

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female patients ≥ 18 years of age
• Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total daily dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis
• Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification"
• Patient in MR4.5 at prescreening at Novartis designated lab
• ECOG performance status of 0-2
• Adequate end organ function as defined by:
• Direct bilirubin ≤ 1.5 x ULN except for i) patients with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range).
• SGOT(AST) and SGPT(ALT) ≤ 3 x ULN i.e. equivalent to ≤ Grade 1 NCI-CTCAE v.4.03
• Serum lipase ≤ 2 x ULN i.e. equivalent to ≤ Grade 2 NCI-CTCAE v.4.03
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum creatinine < 1.5 x ULN
• Patients must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
• Potassium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
• Magnesium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
• Total calcium (corrected for serum albumin)
• Patients must have normal marrow function as defined:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L
• Hemoglobin ≥ 9.0 g/dL
• Platelets ≥ 100 x 10E9/L
• Documented chronic phase CML must meet all the criteria defined by:
• < 15% blasts in peripheral blood and bone marrow,
• < 30% blasts plus promyelocytes in peripheral blood and bone marrow,
• < 20% basophils in the peripheral blood,
• ≥ 100 x 109/L (≥ 100,000/mm3) platelets,
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly

You may not qualify if…

• Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total cumulative duration of 4 weeks
• Previous treatment with alpha-interferon of any duration
• Previous anticancer agents for CML other than nilotinib except for cytoreduction after CML diagnosis until up to 4 weeks after first dose of nilotinib
• Known second chronic phase of CML after previous progression to AP/BC
• Poorly controlled diabetes mellitus (defined as HbA1c > 9%)
• Impaired cardiac function including any one of the following:
• LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher)
• Inability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
• Complete left bundle branch block
• Right bundle branch block plus left anterior or posterior hemiblock
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome or a known family history of long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia
• QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-tested for QTc.This exclusion criterion is not applicable for patients with non-measurable QT interval who have evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
• History or clinical signs of myocardial infarction within 1 year of study entry
• History of unstable angina within 1 year of study entry
• Other clinically significant heart disease (e.g. congestive heart failure, cardiomyopathy or uncontrolled hypertension)
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
• Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, uncontrolled infection)
• History of another active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
• Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1
• Patients who have not recovered from prior surgery
• Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.

Where it is running

• Lakes Research — Miami Lakes, Florida, United States
• H Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• Cancer Center of Kansas — Wichita, Kansas, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Memorial Sloan Kettering — New York, New York, United States
• Oregon Health Sciences University — Portland, Oregon, United States
• Cancer Centers of the Carolinas — Greenville, South Carolina, United States
• Tennessee Oncology PLLC — Chattanooga, Tennessee, United States
• Community Cancer Trials of Utah — Ogden, Utah, United States
• Novartis Investigative Site — Buenos Aires, Argentina
• Novartis Investigative Site — Graz, Austria
• Novartis Investigative Site — Rankweil, Austria
• Novartis Investigative Site — Salzburg, Austria
• Novartis Investigative Site — Vienna, Austria
• Novartis Investigative Site — Vienna, Austria
• Novartis Investigative Site — Sint-Niklaas, Oost Vlaanderen, Belgium
• Novartis Investigative Site — Brussels, Belgium
• Novartis Investigative Site — Brussels, Belgium
• Novartis Investigative Site — Charleroi, Belgium
• Novartis Investigative Site — Ghent, Belgium
• Novartis Investigative Site — Kortrijk, Belgium
• Novartis Investigative Site — Liège, Belgium
• Novartis Investigative Site — Varna, Bulgaria
• Novartis Investigative Site — Bogota, Cundinamarca, Colombia
• Florida Cancer Specialists — Fort Myers, Florida, United States

Full record on ClinicalTrials.gov

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