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Determining the Maximum Tolerated Dose of Low Dose Interferon-alpha in Conjunction With Nilotinib in Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) (NICOLI)

Primary Purpose

Chronic Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Nilotinib, interferon-alfa
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Chronic myeloid leukemia, interferon alfa, nilotinib, combination, CML, Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in chronic phase (CML-CP) after switch from previous CML treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with chronic myeloid leukemia in chronic phase (CML-CP) at screening
  • Initial diagnosis of CML cytogenetically confirmed by the presence of the Ph+ metaphases from the bone marrow
  • Patients who have been treated with nilotinib for a minimum of 6 months (1 month represents 28 days) after switch from previous CML treatments
  • Patients who have been treated with stable dosing of 2x400mg nilotinib within the last month before start of study treatment
  • No grade 3-4 CTC toxicities on nilotinib alone in the last month preceding the start of the study regimen

Exclusion Criteria:

  • Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of the t(9;22) translocation in their bone marrow metaphases
  • Evidence of a point mutation within the BCR-ABL gene leading to a clinically relevant amino acid exchange in the kinase domain at position T315 (gatekeeper mutation T315I)
  • Impaired cardiac function
  • Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nilotinib in conjunction with low dose interferon alfa

Arm Description

Outcomes

Primary Outcome Measures

Number of Clinically significant adverse events or abnormal laboratory values (dose-limiting toxicities) unrelated to disease progression, intercurrent illness, or concomitant medications on the combination treatment

Secondary Outcome Measures

Rate of major cytogenetic response (MCyR) at 6 and 12 months
Rate of complete cytogenetic response (CCyR) at 6 and 12 months
Rate of major molecular response (MMR) at 12 months
Safety profile of nilotinib in combination with interferon alfa, i.e. the number of dose limiting toxicities (DLT) for each interferon alfa dose level
Progression-free survival (PFS)
Event-free survival
Overall survival (OS)

Full Information

First Posted
October 6, 2010
Last Updated
May 1, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01220648
Brief Title
Determining the Maximum Tolerated Dose of Low Dose Interferon-alpha in Conjunction With Nilotinib in Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP)
Acronym
NICOLI
Official Title
An Open Label, Nonrandomized, Single-center, Phase I Trial of Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) With Nilotinib in Combination With Low Dose Interferon-alpha (IFN) - NICOLI Study -
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
This study will assess the maximum tolerated dose of low dose interferon in conjunction with nilotinib in pretreated Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in chronic phase (CML-CP).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
Chronic myeloid leukemia, interferon alfa, nilotinib, combination, CML, Philadelphia chromosome positive (Ph+) chronic myeloid leukemia patients in chronic phase (CML-CP) after switch from previous CML treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib in conjunction with low dose interferon alfa
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nilotinib, interferon-alfa
Other Intervention Name(s)
AMN107
Primary Outcome Measure Information:
Title
Number of Clinically significant adverse events or abnormal laboratory values (dose-limiting toxicities) unrelated to disease progression, intercurrent illness, or concomitant medications on the combination treatment
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Rate of major cytogenetic response (MCyR) at 6 and 12 months
Time Frame
12 months
Title
Rate of complete cytogenetic response (CCyR) at 6 and 12 months
Time Frame
12 months
Title
Rate of major molecular response (MMR) at 12 months
Time Frame
12 months
Title
Safety profile of nilotinib in combination with interferon alfa, i.e. the number of dose limiting toxicities (DLT) for each interferon alfa dose level
Time Frame
12 months
Title
Progression-free survival (PFS)
Time Frame
12 months
Title
Event-free survival
Time Frame
12 months
Title
Overall survival (OS)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with chronic myeloid leukemia in chronic phase (CML-CP) at screening Initial diagnosis of CML cytogenetically confirmed by the presence of the Ph+ metaphases from the bone marrow Patients who have been treated with nilotinib for a minimum of 6 months (1 month represents 28 days) after switch from previous CML treatments Patients who have been treated with stable dosing of 2x400mg nilotinib within the last month before start of study treatment No grade 3-4 CTC toxicities on nilotinib alone in the last month preceding the start of the study regimen Exclusion Criteria: Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of the t(9;22) translocation in their bone marrow metaphases Evidence of a point mutation within the BCR-ABL gene leading to a clinically relevant amino acid exchange in the kinase domain at position T315 (gatekeeper mutation T315I) Impaired cardiac function Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
19959083
Citation
Guilhot F, Roy L, Saulnier PJ, Guilhot J. Interferon in chronic myeloid leukaemia: past and future. Best Pract Res Clin Haematol. 2009 Sep;22(3):315-29. doi: 10.1016/j.beha.2009.10.005.
Results Reference
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Determining the Maximum Tolerated Dose of Low Dose Interferon-alpha in Conjunction With Nilotinib in Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP)

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