Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Bone Marrow Diseases

Leukocyte Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Administered orally as a single agent on a continuous daily schedule given 400 mg bid (twice daily) with food. One cycle comprised of 28 days.

Imatinib

Administered orally as a single agent on a continuous daily schedule of 400 mg bid (2 x 200 mg twice daily) without food. Once cycle comprised of 28 days.

Nilotinib (AMN107)

Novartis Pharmaceuticals

In this study, the efficacy and safety of nilotinib 400 mg twice daily, will be compared with imatinib 400 mg twice daily in patients with a suboptimal response to imatinib for their Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

This trial was to evaluate the CCyR rate at 12 months of nilotinib therapy when compared to imatinib treatment in patients with suboptimal response to imatinib. The patients were stratified by prior duration of initial imatinib treatment, and were randomized to receive either 400 mg/twice daily of continuous nilotinib or imatinib treatment. The first stratum patients were treated with imatinib = 6 to \< 12 months and having at least a minimal cytogenetic, but no partial cytogenetic response; and the second stratum patients were treated with imatinib = 12 months to \< 18 months and having partial cytogenetic response (PCyR), but no CCyR.

Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

A Phase III Randomized, Open- Label Multi-center Study of Nilotinib Versus Imatinib in Adult Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Cytogenetic Response (CyR) on Imatinib

Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.

Patients received 400 mg twice daily, 2 x 200 mg capsules twice daily.

Patients received 400 mg twice daily. Capsules were available in 100 mg and 400 mg formulations.

Total

Age, Categorical

Age Continuous

Sex: Female, Male

Belgium

Germany

Japan

Korea, Republic of

Poland

Region of Enrollment

Study Director

Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib

The trial was terminated early, so only 6 patients were enrolled.

Durable Complete Cytogenetic Response Rate

Overall Study

All patients will receive treatment as follows: imatinib 100 mg tablets, 200 mg daily for 6 months; and nilotinib 150 mg capsule, 300 mg daily for 6 months.

Imatinib and Nilotinib

The purpose of this study is to determine if low-dose imatinib and nilotinib combination, will improve treatment results in CML patients with failure, suboptimal response or intolerance to imatinib therapy.

The hypothesis is that with low-dose imatinib and nilotinib combination, major molecular response will be achieved in patients not previously obtained with imatinib monotherapy.

Low-dose Nilotinib and Imatinib Combination in Chronic Myeloid Leukemia Patients, With Failure, Suboptimal Response or Treatment Intolerance

Low-dose Nilotinib and Imatinib Combination in Chronic Myeloid Leukemia Patients, With Failure, Suboptimal Response or Treatment Intolerance.

Every month adherence will be assessed with a questionnaire

Major molecular response will be evaluated with quantitative Real time polymerase chain reaction assay (RT-PCR)for BCR/ABL at 6 months.

Patients will be evaluated every four weeks to identify possible adverse effects of drugs administered.

Hospital Universitario Dr. Jose E. Gonzalez

Leukemia, Myeloid, Chronic-Phase

Dasatinib

Dasatinib Dasatinib will be administered orally at a dose of 100 mg QD. During the first month, subjects will be instructed to take dasatinib in the morning.

Imatinib Imatinib will be administered orally at a dose of 600 mg once daily (QD). Each 600 mg dose should be administered with a meal and taken with a large glass of water. If a scheduled dose is missed for more than 12 hours or dosing is interrupted for toxicity or for any other reason, these doses should be omitted.

Dasatinib and Imatinib

Jooseop Chung, MD. PhD

Youngjin Choi, MD. PhD

Research Hypothesis:

Treatment with dasatinib 100 mg QD is superior to imatinib 600 mg QD in terms of complete cytogenetic response (CCyR) in chronic phase (CP) Philadelphia chromosome-positive (Ph+) Chronic Myeloid Leukemia (CML) subjects who are imatinib failures or who have achieved only a suboptimal response after 3-18 months (12-77 weeks) of therapy with imatinib 400 mg.

Primary Objective:

The primary objective of this study is to compare the rate of CCyR of dasatinib (100mg QD) to high-dose imatinib (600 mg QD) therapy at 6 months after randomization in CP Ph+ CML subjects who are imatinib failures or who have achieved only a suboptimal response after 3 - 18 months of imatinib monotherapy at 400 mg/day.

Study Design: Prospective open-label, randomized two arms, multicenter study for the patients with suboptimal response to standard Tx to evaluate efficacy \& safety of dasatinib (100mg qd) \& imatinib (600mg daily) by CyR \& MoR at 3, 6 \& 12 months.

* Randomized 1:1
* Crossover to alternate be permitted after confirmed PD at 3M (AP, BC \& loss of CHR or MCyR) \& absence of any response at 6M.

Duration of Study: Subjects will be treated for up to 12 months, unless disease progression or unacceptable toxicity occurs, the subject withdraws, or the study is discontinued.

Duration of Study: Subjects will be treated for up to 12 months, unless disease progression or unacceptable toxicity occurs, the subject withdraws, or the study is discontinued.

Number of Subjects: A total of 90 subjects will be randomized in 1:1 randomization ratio

Study Population: Subjects 18 years of age or older with CP Ph+ CML and who are imatinib failures or ave achieved only a suboptimal response after 3 - 18 months (12 - 77 weeks) of treatment with 400 mg/day of imatinib monotherapy.

Test Product, Dose and Mode of Administration, Duration of Treatment:

Subjects in the dasatinib arm will begin treatment with dasatinib at an oral dose of 100 mg QD. One dose reduction to 70 mg due to toxicity will be allowed. One dose escalation to 140 mg is allowed under specified circumstances.

Reference Therapy, Dose and Mode of Administration, Duration of Treatment:

Subjects in the imatinib arm will begin treatment with imatinib at an oral dose of 600 mg QD Doses of imatinib can be escalated to 800 mg for patients with inadequate response at 3 months and dose reduction of imatinib is not permitted for any cases of patients.

Criteria for Evaluation:

Efficacy:

* Primary Endpoint: CCyR rate at 6 months after randomization.
* Secondary Endpoints:

  * MMR rates at 3, 6, and 12 months
  * CCyR rates at 3, 6 and 12 months
  * CHR rates at 3, 6and 12 months
  * Time to-, and duration of-, MMR and CCyR
  * Progression free survival (PFS)

Safety:

Adverse experiences associated with dasatinib or imatinib treatment will be reported for all treated subjects. Adverse events will be assessed continuously and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.

The Randomized Study of Dasatinib and High-Dose Imatinib (600mg) in Suboptimal Responder

Randomized, Open Label Study of Dasatinib (100mg qd) vs. High-Dose Imatinib (600mg) in Patients With Chronic Phase CML Who Have Had Suboptimal Response After 3-18 Months of Therapy With Imatinib (400mg)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	NCT00519090	Myelogenous Leu...	Imatinib Nilotinib (AMN1...	18 Years -	Novartis
Low-dose Nilotinib and Imatinib Combination in Chronic Myeloid Leukemia Patients, With Failure, Suboptimal Response or Treatment Intolerance	NCT01819389	Leukemia, Myelo...	Imatinib and Ni...	18 Years -	Hospital Universitario Dr. Jose E. Gonzalez
Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	NCT00519090	Myelogenous Leu...	Imatinib Nilotinib (AMN1...	18 Years -	Novartis
The Randomized Study of Dasatinib and High-Dose Imatinib (600mg) in Suboptimal Responder	NCT00854841	Chronic Myeloid...	Dasatinib and I...	18 Years -	Pusan National University Hospital
Low-dose Nilotinib and Imatinib Combination in Chronic Myeloid Leukemia Patients, With Failure, Suboptimal Response or Treatment Intolerance	NCT01819389	Leukemia, Myelo...	Imatinib and Ni...	18 Years -	Hospital Universitario Dr. Jose E. Gonzalez

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