Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

NCT01605981 | Withdrawn Phase 4 DMC

• 1 other identifier: CAMN107EBR06
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 18

Brief Summary

This is an open label, non randomized, prospective, multicenter, phase II clinical trial evaluating nilotinib 400 mg BID for the treatment of newly diagnosed CML-AP patients. Patients enrolled into the study will receive 400mg of nilotinib, orally, twice daily (800mg/day)

Conditions

Chronic Myeloid Leukemia (CML)

Keywords

Nilotinib; CML patients; accelerated phase

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability profile of nilotinib in newly diagnosed CML-AP

  The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.

  12 month

• To test the efficacy of nilotinib 400 mg BID

  To test the efficacy of nilotinib 400 mg BID in inducing complete cytogenetic response (CCyR) at 12 months in newly diagnosed CML-AP patients

  12 months

Secondary Outcomes (5)

• Evaluate the rate of complete hematologic response (CHR)

  3 months

• Evaluate the Quality of Life

  3, 6, 9, 12, 15, 18 and 24 months

• Evaluate the median time to achieve molecular response

  uring the first 2 years of treatment

• Evaluate the proportion of patients achieving CCyR

  3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 months

• To correlate the probability of reaching MMR, CMR and CCyR

  2 years

Study Arms (1)

Nilotinib oral

EXPERIMENTAL

Nilotinib oral dose of 400 mg BID (800 mg/day) continuous dosing for up to 24 months. Nilotinib oral dose of 300 mg BID (600 mg/day) continuous dosing in case of intolerance. Nilotinib oral dose of 400 mg QD (400 mg/day) continuous dosing in case of intolerance

Drug: AMN107

Interventions

AMN107 DRUG

Nilotinib oral

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 age \> 18 years old;
• Diagnosis of Chronic Myeloid leukemia in Accelerated Phase (CML-AP);
• Patients with atypical BCR-ABL transcripts are eligible (transcripts other then b2a2 an b3a2);
• No previous treatment with any antileukemic drugs with the exception of hydroxyurea (HU) and/or anagrelide. In emergent cases where the patient requires disease management while awaiting study start, commercial supplies of Gleevec/Glivec at any dose may be prescribed to the patient but for no longer than 2 weeks in duration;
• ECOG 0,1 or 2;
• Normal serum levels \> LLN (lower limit of normal) or corrected to within normal limits with supplements, prior to the first dose of study medication, of potassium magnesium and calcium;
• AST and ALT \< 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;
• Serum lipase and amylase \< 1.5 x ULN;
• Written informed consent prior to any study procedures being performed.

You may not qualify if:

• Patients in Chronic and Blastic Phases.
• Patients who are considered Ph negative because they do not have a confirmed cytogenetic diagnosis of Philadelphia Ph+ chromosome (9;22 translocation) in \> 20 metaphases.
• Treatment with tyrosine kinase inhibitors or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with the exception of HU and/or anagrelide
• Previously documented T315I mutations;
• Uncontrolled congestive heart failure or hypertension;
• Myocardial infarction or unstable angina pectoris within past 12 months;
• Significant arrhythmias, including history or presence of clinically significant ventricular or atrial tachyarrhythmias, clinically significant bradycardias, long QT syndrome and/or QTc \> 450 msec on screening ECG (using the QTcF formula). Patients with complete LBBB;
• History of confirmed acute or chronic pancreatitis;
• 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 GI 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 bypass surgery);
• Patients with another primary malignancy that is currently clinically significant or requires active intervention;
• Concomitant medications with potential QT prolongation (See link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm);
• Concomitant medications known to interact with CYP450 isoenzymes (CYP 3A4, CYP2C9, CYP2C8, (See link for complete list (http://medicine.iupui.edu/flockhart/table.htm);
• History of significant congenital or acquired bleeding disorder unrelated to cancer;
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Fortaleza, Ceará, 60115-290, Brazil

Location

Novartis Investigative Site

Goiânia, Goiás, 74605-020, Brazil

Location

Novartis Investigative Site

Cuiaba, Mato Grosso do Sul, 033426-102, Brazil

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Novartis Investigative Site

Curitiba, Paraná, 80060-900, Brazil

Location

Novartis Investigative Site

Porto Alegre, Porto Alegre-RS, Brazil

Location

Novartis Investigative Site

Niterói, Rio de Janeiro, 24030210, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20.211-030, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Novartis Investigative Site

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

Novartis Investigative Site

Campinas, São Paulo, 13083-970, Brazil

Location

Novartis Investigative Site

Jaú, São Paulo, 17210-080, Brazil

Location

Novartis Investigative Site

Santo André, São Paulo, 09190-615, Brazil

Location

Novartis Investigative Site

Santos, São Paulo, 11075-350, Brazil

Location

Novartis Investigative Site

São José, São Paulo, 15015-110, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05651-901, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 08270-070, Brazil

Location

Novartis Investigative Site

São Paulo, 03454-000, Brazil

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

Study Officials

• Novartis Biociências SA - Brazil

  Novartis

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: May 25, 2012
• Study Start: February 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: April 20, 2017

Record last verified: 2014-06

Locations

BR (18)