Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib

NCT01400074 | Unknown Phase 3 DMC

• 1 other identifier: CAMN107AKR01T
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the efficacy of nilotinib at 400 mg BID will be compared with imatinib at 400 mg BID in suboptimal molecular response patients. To determine study eligibility, suboptimal molecular response will be defined as patients who have achieved a complete cytogenetic response (CCyR) but have not achieved a MMR, after at least 18 months of treatment on first line imatinib therapy at a minimum dose of 400mg daily (Baccarani 2006).

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• the cumulative rate of MMR

  To evaluate the cumulative rate of MMR at 12 months of nilotinib compared to imatinib in adult patients with Ph+ CML in early CP who have suboptimal molecular response to imatinib

  12 months

Study Arms (2)

Nilotinib

ACTIVE COMPARATOR

400 mg twice daily

Drug: Nilotinib, Imatinib

Imatinib

ACTIVE COMPARATOR

400 mg twice daily

Drug: Nilotinib, Imatinib

Interventions

Nilotinib, Imatinib DRUG

Nilotinib: 400 mg twice daily Imatinib: 400 mg twice daily

Also known as: Nilotinib (AMN107): Tasigna, Imatinib (STI571): Gleevec

Imatinib; 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
• ECOG 0, 1, or 2
• Diagnosis of Ph+ CML in CP
• Patients with suboptimal molecular response defined as:
• Patients must achieve a CCyR at 12 months and must maintain CCyR until study entry (0% Ph+ chromosomes). Cytogenetic confirmation of Ph+ (9;22 translocation) is required on a minimum of 20 metaphases. FISH analysis will not be accepted.
• at least 18 months and up to 24 months (≥18 to ≤24 months) of treatment with imatinib as first line therapy, at a dose of 400 mg daily, without achieving a MMR (\<0.1% IS of Bcr-Abl transcript by RQ- PCR).
• The following laboratory results must be present:
• Total bilirubin \<1.5 x ULN
• SGOT and SGPT \<2.5 x ULN
• Creatinine \<1.5 x ULN
• Serum amylase and lipase ≤ 1.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
• Serum potassium, magnesium and calcium ≥ LLN or correctable with supplements to within normal limits prior to the first dose of study medication.
• Ability to provide written informed consent prior to any study related screening procedures being performed.

You may not qualify if:

• Late CP who started imatinib more than 6 months after diagnosis
• Prior accelerated phase or blast phase CML
• Rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose galactose malabsorption
• Hypersensitivity to nilotinib or any of the excipients.
• Previously documented T315I mutations.
• Intolerance to imatinib 400 mg daily defined as the inability to maintain at least 400 mg daily for the previous 3 months.
• Patients treated with imatinib more than 400mg daily
• Achieved prior MMR or CCyR on imatinib and lost response to entering the study.
• Previous treatment with interferon or any other tyrosine kinase inhibitor except imatinib (however, allow hydroxyurea or anagrelide before initial imatinib start)
• Impaired cardiac function
• Treatment with inhibitors of CYP3A4 or medications well documented to prolong the QT interval are contraindicated
• Impaired gastrointestinal (GI) function or GI disease
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
• Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
• Any other malignancy that is clinically significant or requires active intervention.

Sponsors & Collaborators

• Seoul St. Mary's Hospital: lead
• Novartis: collaborator

Study Sites (1)

Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; Imatinib Mesylate

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Dong-Wook Kim, MD, PhD

  Seoul St. Mary's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sahee Park, MS

CONTACT

+82-2-2258-7030; saheepark@catholic.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 21, 2011
• First Posted: July 22, 2011
• Study Start: January 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: January 13, 2014

Record last verified: 2014-01

Locations

KR (1)