A study of full treatment-free remission in patients with chronic myeloid leukemia treated with nilotinib

Phase 1

• Conditions: Patients with chronic myeloid leukemia in chronic phase treated with nilotinib in first-line therapy who have achieved a sustained, deep molecular response for at least 1 year.; MedDRA version: 21.0Level: LLTClassification code 10054352Term: Chronic phase chronic myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002898-21-IT
• Lead Sponsor: OVARTIS FARMA S.P.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-21
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

1. Male and female patients 18 years or older.
2. Diagnosis of CML-CP according to the World Health Organization.
3. Patients with CML-CP under treatment with nilotinib at the approved daily dose of 300 mg BID mg for at least 3 calendar years.
4. Sustained DMR for at least one year at screening, defined as MR4.5 (BCR-ABL level = 0.0032% IS) or undetectable MR4.0 (undetectable BCR-ABL level (IS) with assay sensitivity of 4.0 log in 3 of the last 4 quarterly BCR-ABL RQ-PCR assessments, and with the last assessment also in MR4.5 or undetectable MR4.0.
5. Patient must meet the following laboratory values at the screening visit:
• Absolute Neutrophil Count =1.5 x 109/L
• Platelets =75 x 109/L
• Hemoglobin (Hgb) = 9 g/dL
• Serum creatinine < 1.5 mg/dL
• Total bilirubin = 1.5 x ULN
• Aspartate transaminase (AST) = 3.0 x ULN
• Alanine transaminase (ALT) = 3.0 x ULN
• Serum lipase = 2 x ULN
6. Eastern Cooperative Oncology Group performance status 0-2.
7. Study subjects must be able to comply with study procedures and follow-up examinations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

1. Patients with known atypical transcript.
2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past).
3. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months.
4. Patient ever attempted to permanently discontinue imatinib or nilotinib treatment.
5. Known impaired cardiac function including any one of the following:
• Inability to determine QT interval on ECG
• Complete left bundle branch block
• 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
• QTcF > 480 msec
• History or clinical signs of myocardial infarction within 1 year prior to study entry
• History of unstable angina within 1 year prior to study entry
• Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)
6. 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.
7. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis.
8. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer.
9. History of other active malignancy within 5 years prior to study entry except for previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively.
10. Patients who have not recovered from prior surgery.
11. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1.
12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
13. 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 study entry.
14. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.
15. Pregnant or nursing (lactating) women.
16. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 14 days after stopping medication. There is a limited amount of data on pregnancies in patients while attempting treatment-free remission (TFR). If pregnancy is planned during the TFR phase, the patient must be informed of a potential need to re-initiate treatment with nilotinib during pregnancy.
For further exclusion criteria please refer to the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified