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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00519090
• Collaborator: (none)
• Enrollment: 6
• Locations: 80
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Myelogenous Leukemia	Drug: Imatinib; Drug: Nilotinib (AMN107)	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib (AMN107)	Drug: Nilotinib (AMN107); 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.
Active Comparator: Imatinib	Drug: Imatinib; 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.; Other Names: STI571 imatinib mesylate Glivec® Gleevec®

Outcome Measures

Primary Outcome Measures

1. Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib [12 months]

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

Secondary Outcome Measures

1. Durable Complete Cytogenetic Response Rate [24 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Diagnosis of Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase.

Patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as:

• 6 to < 12 months of treatment and -have 36 - 95% Ph+ metaphases, or

• 12 to <18 months of treatment and have 1 - 35% Ph+ metaphases (Standard cytogenetics, no FISH [fluorescence in situ hybridization] analysis was allowed).

Exclusion criteria:

• Patient who have received more than 18 months of imatinib therapy

• Patients who have achieved partial or complete cytogenetic response and lost that response prior to entering the study.

• Prior treatment with greater than 400 mg/day imatinib.

• Uncontrolled or significant cardiovascular disease.

• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).

• Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)

• Currently taking certain medications that could affect the rhythm of your heart.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85701
2	Southern California Permanente Medical Group	Anaheim	California	United States	92801
3	Southern California Permanente Medical Group	Baldwin Park	California	United States	91706
4	Southern California Permanente Medical Group	Fontana	California	United States	92334
5	Kaiser Permanente Medical Group/Hayward Medical Center	Hayward	California	United States	94540
6	Southern California Permanente Medical Group	Los Angeles	California	United States	90001
7	Kaiser Permanente Medical Group/Oakland Medical Center	Oakland	California	United States	94601
8	Southern California Permanente Medical Group	Panorama City	California	United States	91402
9	Southern California Permanente Medical Group	Riverside	California	United States	92501
10	Kaiser Permanente Medical Group/South San Francisco Medical Center	S. San Francisco	California	United States	94101
11	Kaiser Permanente Medical Group/Sacramento Medical Center	Sacramento	California	United States	94203
12	Southern California Permanente Medical Group	San Diego	California	United States	92101
13	Kaiser Permanente Medical Group	San Francisco	California	United States	94101
14	Kaiser Permanente Medical Group	San Jose	California	United States	95101
15	Kaiser Permanente Medical Group/Santa Clara Medical Office	Santa Clara	California	United States	95050
16	Kaiser Permanente Medical Group/Vallejo Medical Center	Vallejo	California	United States	94589
17	Kaiser Permanente Medical Group/Walnut Creek Medical Center	Walnut Creek	California	United States	94595
18	Southen California Permanente Medical Group	Woodland Hills	California	United States	91364
19	Rocky Mountain Cancer Center	Denver	Colorado	United States	80201
20	Northwestern Memorial Hospital	Chicago	Illinois	United States	60601
21	The University of Chicago Medical Center	Chicago	Illinois	United States	60601
22	Indiana Blood and Marrow Transplantation	Beech Grove	Indiana	United States	46107
23	Holden Cancer Center	Iowa City	Iowa	United States	52240
24	Johns Hopkins Hospital	Baltimore	Maryland	United States	21201
25	University of Michigan	Ann Arbor	Michigan	United States	48103
26	Hematology Centers of Western Michigan	Grand Rapids	Michigan	United States	49501
27	Methodist Cancer Center	Omaha	Nebraska	United States	68101
28	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
29	Duke University Hospital	Durham	North Carolina	United States	27701
30	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27101
31	Oregon Health Sciences University	Portland	Oregon	United States	97201
32	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania	United States	18015
33	Jones Cancer Center	Germantown	Tennessee	United States	38138
34	Vanderbilt University	Nashville	Tennessee	United States	37201
35	University of Texas/MD Anderson Cancer Center	Houston	Texas	United States	77001
36	Swedish Cancer Institute	Seattle	Washington	United States	98101
37	Novartis Investigative Site	Darlinghurst		Australia
38	Novartis Investigative Site	Herston		Australia
39	Novartis Investigative Site	Liverpool		Australia
40	Novartis Investigative Site	Perth		Australia
41	Novartis Investigative Site	Prahran		Australia
42	Novartis Investigative Site	South Brisbane		Australia
43	Novartis Investigative Site	St. Leonards		Australia
44	Novartis Investigative Site	Brugge		Belgium
45	Novartis Investigative Site	Gent		Belgium
46	Novartis Investigative Site	Leuven		Belgium
47	Novartis Investigative Site	Mannheim		Brazil
48	Novartis Investigative Site	Porto Alegre		Brazil
49	Novartis Investigative Site	Sao Paulo		Brazil
50	Novartis Investigative Site	Olomouc		Czech Republic
51	Novartis Investigative Site	Praha		Czech Republic
52	Novartis Investigative Site	Berlin		Germany
53	Novartis Investigative Site	Duesseldorf		Germany
54	Novartis Investigative Site	Eisensach		Germany
55	Novartis Investigative Site	Firenze		Germany
56	Novartis Investigative Site	Griefswald		Germany
57	Novartis Investigative Site	Hamburg		Germany
58	Novartis Investigative Site	Jena		Germany
59	Novartis Investigative Site	Kiel		Germany
60	Novartis Investigative Site	Leipzeg		Germany
61	Novartis Investigative Site	Postsdam		Germany
62	Novartis Investigative Site	Rostock		Germany
63	Novartis Investigative Site	Stuttgart		Germany
64	Novartis Investigative Site	Weiden		Germany
65	Novartis Investigative Site	Bologna		Italy
66	Novartis Investigative Site	Milano		Italy
67	Novartis Investigative Site	Napoli		Italy
68	Novartis Investigative Site	Orbassano		Italy
69	Novartis Investigative Site	Reggio Calabra		Italy
70	Novartis Investigative Site	Roma		Italy
71	Novartis Investigative Site	Nagoya		Japan
72	Novartis Investigative Site	Oaska		Japan
73	Novartis Investigative Site	Tokyo		Japan
74	Novartis Investigative Site	Hwasun-Gun		Korea, Republic of
75	Novartis Investigative Site	Seoul		Korea, Republic of
76	Novartis Investigative Site	Barcelona		Spain
77	Novartis Investigative Site	Madrid		Spain
78	Novartis Investigative Site	Salamanca		Spain
79	Novartis Investigative Site	Santiago de Compostela		Spain
80	Novartis Investigative Site	Valencia		Spain

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00519090
• Other Study ID Numbers: CAMN107A2302
• First Posted: Aug 21, 2007
• Last Update Posted: Nov 6, 2011
• Last Verified: Nov 1, 2011

• Keywords provided by Novartis Pharmaceuticals: leukemia; bone marrow; leukemia symptoms; cml; complete blood count; lymphocyte; blood cancer; leukocytes; chronic leukemia; bone marrow biopsy; leukemia research; leukemia cells; bone marrow disease; chronic myeloid leukemia; blood cancer symptoms; white blood cell diseases; chronic myelogenous leukemia; leukemia treatment; leukemia facts; leucemia; facts about leukemia; myelogenous leukemia; newly diagnosed CML; suboptimal response; Philadelphia chromosome positive (Ph+); chronic myelogenous leukemia in chronic phase (CML-CP)
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Nilotinib (AMN107)	Imatinib
Arm/Group Description	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.
Period Title: Overall Study
STARTED	2	4
COMPLETED	2	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nilotinib (AMN107)	Imatinib	Total
Arm/Group Description	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 of all reporting groups
Overall Participants	2	4	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	4 100%	4 66.7%
>=65 years	2 100%	0 0%	2 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.5 (4.949747)	45.5 (12.06924)	54 (15.6812)
Sex: Female, Male (Count of Participants)
Female	1 50%	3 75%	4 66.7%
Male	1 50%	1 25%	2 33.3%
Region of Enrollment (participants) [Number]
Belgium	1 50%	0 0%	1 16.7%
Germany	0 0%	1 25%	1 16.7%
Japan	1 50%	0 0%	1 16.7%
Korea, Republic of	0 0%	1 25%	1 16.7%
Poland	0 0%	2 50%	2 33.3%

Outcome Measures

1. Primary Outcome

Title	Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib
Description	Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib (AMN107)	Imatinib
Arm/Group Description	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Durable Complete Cytogenetic Response Rate
Description	Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Nilotinib (AMN107)	Imatinib
Arm/Group Description	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.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Nilotinib (AMN107)		Imatinib
Arm/Group Description	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.
All Cause Mortality
	Nilotinib (AMN107)		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nilotinib (AMN107)		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Nilotinib (AMN107)		Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anaemia	1/2 (50%)		0/4 (0%)
Leukopenia	0/2 (0%)		1/4 (25%)
Neutropenia	0/2 (0%)		1/4 (25%)
Thrombocytopenia	0/2 (0%)		2/4 (50%)
Eye disorders
Periorbital Oedema	0/2 (0%)		2/4 (50%)
Gastrointestinal disorders
Constipation	1/2 (50%)		0/4 (0%)
General disorders
Fatigue	1/2 (50%)		0/4 (0%)
Hepatobiliary disorders
Hepatic function abnormality	1/2 (50%)		0/4 (0%)
Hyperbilirubinemia	0/2 (0%)		1/4 (25%)
Infections and infestations
Herpes simplex	0/2 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Arthropod bite	1/2 (50%)		0/4 (0%)
Metabolism and nutrition disorders
Hypophosphataemia	0/2 (0%)		1/4 (25%)
Weight decrease	1/2 (50%)		0/4 (0%)
Weight increase	0/2 (0%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/2 (0%)		2/4 (50%)
Myalgia	1/2 (50%)		0/4 (0%)
Nervous system disorders
Headache	0/2 (0%)		2/4 (50%)
Respiratory, thoracic and mediastinal disorders
Cough	1/2 (50%)		0/4 (0%)
Dyspnoea	1/2 (50%)		1/4 (25%)
Nasopharyngitis	1/2 (50%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Face Oedema	0/2 (0%)		1/4 (25%)
Rash	1/2 (50%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data in the clinical trial.