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)

Chronic Myeloid Leukemia Clinical Trial

— 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 -

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01220648
• Other study ID #: CAMN107ADE10
• Secondary ID: 2010-022006-40
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2010
• Last updated: May 1, 2015
• Start date: April 2012
• Est. completion date: January 2014

Study information

• Verified date: May 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome

Intervention

Drug:
• Nilotinib, interferon-alfa

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Leipzig

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		12 months	Yes
Secondary	Rate of major cytogenetic response (MCyR) at 6 and 12 months		12 months	No
Secondary	Rate of complete cytogenetic response (CCyR) at 6 and 12 months		12 months	No
Secondary	Rate of major molecular response (MMR) at 12 months		12 months	No
Secondary	Safety profile of nilotinib in combination with interferon alfa, i.e. the number of dose limiting toxicities (DLT) for each interferon alfa dose level		12 months	Yes
Secondary	Progression-free survival (PFS)		12 months	Yes
Secondary	Event-free survival		12 months	Yes
Secondary	Overall survival (OS)		12 months	Yes