Trial to Evaluate the Improvement of Chronic Low-grade AEs in Patients With Ph+ CML With Optimal Response to Imatinib When Switched to Nilotinib

NCT02115386 | Terminated Phase 3 Results

• 1 other identifier: CAMN107ARU02
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective for this study is to evaluate changes in chronic low grade non-hematological adverse events experienced by patients who have been treated with at least 6 months of imatinib and who have not responded to supportive measures, when they are switched to nilotinib (CTCAE grading system).

Conditions

Philadelphia Positive (Ph+) Chronic Myeloid Leukemia

Keywords

Ph+ CML, chronic myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Improvement of Grades of Persistent Non-hematological Adverse Event (AE) for Grade 1 and 2 at 6 Months

  Improvement was defined as decreasing of grade of non-hematological toxicity from 2 to \<2 or from 1 to \<1. In case of multiple low-grade non-hematological toxicities improvement was defined as an improvement of at least one non-hematological AE and no worsening of any other persistent non-hematological AEs.

  at 6 month after switching from imatinib to nilotinib

Secondary Outcomes (6)

• Number of Participants With Improvement of Grades of Persistent Non-hematological Adverse Event (AE) for Grade 1 and 2 at 3 Months

  at 3 month after switching from imatinib to nilotinib

• Number of Participants With Complete Cytogenetic Response (CCyR)

  at months 6,12 and 24 after switching from imatinib to nilotinib

• Number of Participants With a Major Molecular Response

  Months 1, 3, 6, early termination

• Time to and Duration of CCyR and MMR After Switch From Imatinib to Nilotinib at 24 Months

  at 24 Months

• Time to First Improvement of Persistant Chronic Low-grade Non-hematologic AEs at 24 Months After Switch From Imatinib to Nilotinib

  first improvement of AEs after switch to 24 Months

Study Arms (1)

Nilotinib

EXPERIMENTAL

Dosage was 300 mg BID daily taken orally without food.

Drug: Nilotinib

Interventions

Nilotinib DRUG

supplied in 150 mg capsules to be taken orally

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age 2. ECOG ≤ 2 3. Diagnosis of CML-CP \< 15% blasts in peripheral blood and bone marrow
• \< 30% blasts plus promyelocytes in peripheral blood and bone marrow
• \< 20% basophiles in the peripheral blood
• ≥ 100 x 109 /L platelets
• Patients treated with imatinib for ≥6 and \<12 months must be in MCR Patients treated with imatinib for ≥12 and \<18 months must be in CCR
• Total bilirubin \< 1.5 x ULN
• AST and ALT \< 2.5 x ULN
• Creatinine \< 1.5 x ULN
• Serum amylase and lipase ≤ 1.5x ULN
• Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related 11. Serum potassium, magnesium, phosphorus and calcium values within normal range or corrected to within normal limits with supplements prior to first dose of study medication. 12. Patients must have an imatinib washout period of at least 3 days and not to exceed 7 days prior to the first dose of nilotinib. 13. Ability to provide written informed consent prior to any study related screening procedures being done

You may not qualify if:

• Patients who have experienced any Grade 3 or higher non-hematologic toxicity 30 days prior to screening
• Prior accelerated phase or blast phase CML
• Previously documented T315I mutation
• Chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
• Previous treatment with any other tyrosine kinase inhibitors except for only imatinib
• Impaired cardiac function including any of the following:
• LVEF \< 45% as determined by echocardiogram reading or MUGA
• Complete left bundle branch block
• Long QT syndrome or a known family history of long QT syndrome
• History or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (\< 50 beats per minute)
• QTcF \> 450 msec on baseline ECG. If QTcF \> 450 and electrolytes are not within normal ranges, electrolytes were to be corrected and then the patient re-screened for QTcF
• Myocardial infarction within 1 year of starting study drug
• Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension) 9. Patients receiving therapy with inhibitors of CYP3A4 or medications that prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. 10. Treatment with strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort), that cannot be discontinued or switched to a different medication prior to starting study drug. 11. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 12. History of acute pancreatitis within 1 year of study entry. 13. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). 14. Any other malignancy that is clinically significant or requires active intervention.
• \. Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, active or uncontrolled infection). 16. Acute or chronic liver or severe renal disease considered unrelated to cancer.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Moscow, 125167, Russia

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

(862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: December 17, 2015
• Primary Completion: October 31, 2016
• Study Completion: October 31, 2016
• Last Updated: December 10, 2019
• Results First Posted: December 10, 2019

Record last verified: 2019-12

Locations

RU (1)