Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)

• Sponsor: Ariad Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01650805
• Collaborator: (none)
• Enrollment: 307
• Locations: 170
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of ponatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: ponatinib; Drug: imatinib (Gleevec/ Glivec)	Phase 3

Detailed Description

This multicenter, international, phase 3 trial will test the hypothesis that ponatinib is an effective treatment for newly diagnosed CP-CML patients when compared with standard imatinib.

Patients will be randomized in a 1:1 fashion, stratified by Sokal risk score at diagnosis (low, intermediate, high), to receive once daily oral administration of either ponatinib or imatinib. Efficacy measures include molecular, cytogenetic, and hematologic response rates at various timepoints; time to, duration of, and durability of responses; and survival follow-up. Safety measures include clinical laboratory testing, adverse event monitoring, vital signs, physical exams, ECGs, and ECHOs. Other measures include two patient-reported health outcomes questionnaires (FACT-Leu and EQ-5D-5L), determination of mutation status, and, for ponatinib only, measurement of steady-state plasma concentration. Accrual is expected to take approximately 2 years, and patients will be followed for survival for up to 8 years after the last patient's first dose; therefore, patient participation may last up to 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ponatinib	Drug: ponatinib; 45 mg tablet, taken orally once daily
Active Comparator: imatinib	Drug: imatinib (Gleevec/ Glivec); 400 mg tablet, taken orally once daily

Outcome Measures

Primary Outcome Measures

1. Major Molecular Response (MMR) Rate at 12 Months [12 months after first dose]

   A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.

Secondary Outcome Measures

1. MMR Rate [5 years after first dose]

   To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years

2. <10% BCR-ABL^IS Rate [3 months after first dose]

   To compare the proportion of patients achieving a ratio of <10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (<10% BCR-ABL^IS), in patients administered ponatinib versus those administered imatinib

3. Complete Cytogenetic Response (CCyR) Rate [12 months after first dose]

   The percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. Responses are defined as follows: Complete (CCyR): 0% Ph+ metaphases.

4. Progression-free Survival [Up to 8 years after the last patient's first dose]

   To compare, according to treatment with ponatinib versus imatinib, progression-free survival

5. Overall Survival [Up to 8 years after the last patient's first dose]

   To compare, according to treatment with ponatinib versus imatinib, overall survival

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. CP CML within 6 months of diagnosis

• CP-CML will be defined by (i) <15% blasts in bone marrow; (ii) <30% blasts plus promyelocytes in bone marrow; (iii) <20% basophils in peripheral blood; (iv) ≥100 × 10^{9/L platelets (≥100,000/mm}3); (v) No evidence of extramedullary disease except hepatosplenomegaly; AND (vi) No prior diagnosis of AP-CML or BP-CML

1. Cytogenetic assessment must demonstrate the BCR-ABL fusion by presence of the t(9;22) Philadelphia chromosome

• (a)Variant translocations are only allowed provided they are assessable for cytogenetic response utilizing conventional cytogenetic techniques; (b) Conventional chromosome banding must be performed; AND (c) A minimum of 20 metaphases must be assessable at entry

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

2. Adequate hepatic function as defined by the following criteria:

(a) Total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome; (b) Alanine aminotransferase (ALT) ≤2.5 × ULN; AND (c) Aspartate aminotransferase (AST) ≤2.5 × ULN

1. Adequate renal function as defined as defined by serum creatinine <1.5 x ULN

2. Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN

Exclusion Criteria:

1. Received prior imatinib therapy

2. Received prior dasatinib therapy

3. Received prior nilotinib therapy

4. Received, for CML, any other systemic anticancer therapy, experimental therapy, or radiation therapy with the exception of anagrelide or hydroxyurea

5. Major surgery within 28 days prior to initiating therapy

6. History of bleeding disorder unrelated to CML

7. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis

8. History of alcohol abuse

9. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)

10. Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:

11. Myocardial infarction, within 6 months prior to randomization

12. Unstable angina within 6 months prior to randomization

13. Congestive heart failure within 6 months prior to randomization

14. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia

15. Any history of ventricular arrhythmia

16. Cerebrovascular accident or transient ischemic attack within 6 months prior to randomization

17. Any history of peripheral arterial occlusive disease requiring revascularization

18. Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism

19. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control

20. Taking medications that are known to be associated with Torsades de Pointes

21. Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection

22. Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history

23. Pregnant or breastfeeding

24. Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs

25. Diagnosed with or received anticancer therapy for another primary malignancy within 3 years prior to entry (except for non-melanoma skin cancer or cervical cancer in situ)

26. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US Oncology - Providence Health System, Site #167	Burbank	California	United States	91505
2	UCLA Department of Medicine, Site #027	Los Angeles	California	United States	90095
3	Bay Area Cancer Research Group, Site #156	Pleasant Hill	California	United States	94523
4	Bay Area Cancer Research Group, Site #157	Pleasant Hill	California	United States	94523
5	Rocky Mountain Cancer Centers, Site #191	Boulder	Colorado	United States	80303
6	Cancer Center of Central Connecticut, Site #147	Southington	Connecticut	United States	06489
7	Christiana Care Health Services, Site #155	Newark	Delaware	United States	19713
8	University Cancer Institute, Site #149	Boynton Beach	Florida	United States	33426
9	Florida Cancer Specialists, Site #180	Fort Meyers	Florida	United States	33916
10	Florida Cancer Specialists, Site #179	St. Petersburg	Florida	United States	33705
11	Emory University, Site #058	Atlanta	Georgia	United States	30322
12	John H. Stroger, Jr. Hospital of Cook County, Site #192	Chicago	Illinois	United States	60612
13	University of Chicago, Site #001	Chicago	Illinois	United States	60637
14	Loyola University Chicago, Site #054	Maywood	Illinois	United States	60153
15	Franciscan St. Francis Health, Site #138	Indianapolis	Indiana	United States	46237
16	University of Iowa Hospitals and Clinics, Site #050	Iowa City	Iowa	United States	52242
17	Siouxland Hematology-Oncology Associates, Site #198	Sioux City	Iowa	United States	51101
18	US Oncology - Cancer Center of Kansas, Site #168	Wichita	Kansas	United States	67214
19	Willis-Knighton Cancer Center, Site #196	Shreveport	Louisiana	United States	71103
20	University of Maryland, Greenebaum Cancer Center, Site #040	Baltimore	Maryland	United States	21201
21	Greater Baltimore Medical Center, Site #140	Baltimore	Maryland	United States	21204
22	St. Agnes Healthcare, Site #185	Baltimore	Maryland	United States	21229
23	Massachusetts General Hospital, Site #047	Boston	Massachusetts	United States	02114
24	Dana Farber Cancer Institute, Site #008	Boston	Massachusetts	United States	02215
25	University of Massachusetts Worcester, Site #152	Worcester	Massachusetts	United States	01655
26	University of Michigan Medical Center, Site #011	Ann Arbor	Michigan	United States	48109
27	Providence Cancer Institute, Site #197	Southfield	Michigan	United States	48075
28	Mayo Clinic, Site #044	Rochester	Minnesota	United States	55905
29	Oncology Research Park Nicollet Institute, Site #195	St. Louis Park	Minnesota	United States	55426
30	Saint Luke's Hospital, Site #162	Kansas City	Missouri	United States	64111
31	Mercy Clinic - Cancer & Hematology, Site #151	Springfield	Missouri	United States	65804
32	Nebraska Hematology-Oncology, P.C., Site # 133	Lincoln	Nebraska	United States	68506
33	US Oncology - Comprehensive Cancer Center of Nevada, Site #169	Las Vegas	Nevada	United States	89169
34	John Theurer Cancer Center, Site #128	Hackensack	New Jersey	United States	07601
35	University of New Mexico Cancer Center, Site #166	Albuquerque	New Mexico	United States	87106
36	Maimonides Cancer Center, Site #177	Brooklyn	New York	United States	11220
37	Winthrop University Hospital, Site #153	Mineola	New York	United States	11501
38	Beth Israel Medical Center, Site #145	New York	New York	United States	10003
39	Mount Sinai School of Medicine, Site #189	New York	New York	United States	10029
40	Memorial Sloan-Kettering Cancer Center, Site #078	New York	New York	United States	10065
41	Weill Cornell Medical College, Site #006	New York	New York	United States	10065
42	New York Medical College, Site #146	Valhalla	New York	United States	10595
43	Southeastern Medical Oncology Center, Site #188	Goldsboro	North Carolina	United States	27534
44	Signal Point Clinical Research Center, Site #139	Middletown	Ohio	United States	45042
45	University of Oklahoma, Site #028	Oklahoma City	Oklahoma	United States	73104
46	Providence Cancer Center Oncology and Hematology Care Eastside, Site #194	Portland	Oregon	United States	97213
47	Kaiser Permanente Northwest, Site #200	Portland	Oregon	United States	97227
48	Oregon Health & Science University, Site #048	Portland	Oregon	United States	97239
49	Gettysburg Cancer Center, Site #160	Gettysburg	Pennsylvania	United States	17325
50	Western Pennsylvania Hospital, Site #159	Pittsburgh	Pennsylvania	United States	15224
51	Medical University of South Carolina, Site #148	Charleston	South Carolina	United States	29425
52	Carolina Hematology Oncology, Site #143	Sumter	South Carolina	United States	29150
53	Associates in Oncology & Hematology, Site #186	Chattanooga	Tennessee	United States	37421
54	Sarah Cannon Research Institute, Site #076	Nashville	Tennessee	United States	37203
55	US Oncology - Texas Oncology Austin, Site #172	Austin	Texas	United States	78705
56	US Oncology - Texas Oncology Dallas, Site #171	Dallas	Texas	United States	75231
57	University of Texas Southwestern Medical Center, Site #178	Dallas	Texas	United States	75390
58	Baylor College of Medicine, Site #063	Houston	Texas	United States	77030
59	US Oncology - Texas Oncology Midland, Site #173	Midland	Texas	United States	79701
60	US Oncology - Cancer Care Center of South Texas, Site #170	San Antonio	Texas	United States	78229
61	Huntsman Cancer Institute, Site #043	Salt Lake City	Utah	United States	84112
62	VCU Massey Cancer Center, Dalton Oncology Clinic, Site #069	Richmond	Virginia	United States	23298
63	Seattle Cancer Care Alliance, Site #100	Seattle	Washington	United States	98109
64	US Oncology - Northwest Cancer Specialists, Site #174	Vancouver	Washington	United States	98684
65	West Virginia University, Site #154	Morgantown	West Virginia	United States	26506
66	Green Bay Oncology, Ltd. / St. Mary's Hospital Medical Center, Site #193	Green Bay	Wisconsin	United States	54303
67	University of Wisconsin, Site #030	Madison	Wisconsin	United States	53792
68	Canberra Hospital, Site #971	Garran	Australian Capital Territory	Australia	2605
69	Royal North Shore Hospital, Site #941	Sydney	New South Wales	Australia	2065
70	Royal Adelaide Hospital, Site #951	Adelaide	South Australia	Australia	5000
71	The Peter MacCallum Cancer Center, Site #950	East Melbourne	Victoria	Australia	3002
72	Box Hill Hospital, Site #940	Melbourne	Victoria	Australia	3128
73	Royal Perth Hospital, Site #972	Perth	Western Australia	Australia	6000
74	Medizinische Universitat Wien / AKH, Universitatsklinik fur Inniere Medizin I, Site #561	Wien		Austria	01090
75	UZ Brussel - Department Hematology, Site #544	Brussel		Belgium
76	Clinique Universitaire de Saint-Luc, Department of Haematology, Site #508	Bruxelles		Belgium	3000
77	UZ Gent - Department Hematology, Site #756	Gent		Belgium
78	UZ Gasthuisberg - Department of Hematology, Site #700	Leuven		Belgium	3000
79	University Health Network, Princess Margaret Hospital, Site #083	Toronto	Ontario	Canada	M5G 2M9
80	Jewish General Hospital, Site #129	Montreal	Quebec	Canada	H3T 1E2
81	Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika, Site #514	Brno		Czech Republic	62500
82	FN Hradec Kralove, Site #517	Hradec Kralove		Czech Republic	50005
83	Fakultni nemocnice Olomouc, Hematoonkologicka klinika, Site #515	Olomouc		Czech Republic	77520
84	Ustav hematologie a krevni transfuse, Site #516	Praha		Czech Republic	12808
85	Helsinki University Central Hospital, Site #542	Helsinki		Finland
86	Institut Bergonie, Site #772	Bordeaux		France
87	CHRU de Brest, Hopital Morvan, Site #523	Brest		France	29200
88	CHU Henri Mondor, Site #520	Creteil Cedex		France	94010
89	Centre Hospitalier de Versailles, Site #958	Le Chesnay Cedex		France
90	Hospital Claude Huriez, Site #952	Lille Cedex		France	59037
91	Institut Paoli Calmette, Site #519	Marseille		France
92	CHU de Brabois, Site #953	Nancy Cedex		France
93	CHU de Nantes, Site #521	Nantes Cedex		France	44093
94	Service Hematologie - Hospital Archet I, Site #509	Nice Cedex		France	06202
95	Hopital Saint-Louis, Site #957	Paris		France	75475
96	Hospital Saint Antoine, Site #518	Paris		France
97	Centre Hospitalier Lyon Sud, Site #956	Pierre Benite		France	69495
98	CHU de Poitiers, Site #954	Poitiers		France	86021
99	CHU Purpan, Site #955	Toulouse Cedex		France
100	Universitätsklinikum Aachen, AÖR, Site #513	Aachen		Germany	52074
101	Charite - Universitatsmedizin Berlin, Site #701	Berlin		Germany	13353
102	Universitatsklinikum Carl Gustav Carus an der TU Dresden, Site #526	Dresden		Germany	01307
103	Universitatsklinikum Freiburg, Site #527	Freiburg		Germany
104	Universitatsklinikum Hamburg-Eppendorf, Site #524	Hamburg		Germany	20246
105	Universitatsklinikum Jena, Site #946	Jena		Germany	07747
106	Universitatsklinikum Koln-AOR, Site #525	Koln		Germany	50937
107	Universitat Heidelberg, CML - Studienzentrale III. Medizinische Klinik, Site #947	Mannheim		Germany	68167
108	Klinikum rechts der Isar, Site #949	Munchen		Germany	81675
109	Prince of Wales Hospital, Site #974	Hong Kong		Hong Kong
110	Queen Mary Hospital, Site #973	Hong Kong		Hong Kong
111	Unita Operativa di Ematologia con Trapianto, Site #529	Bari		Italy	70124
112	Istituto di Ematologia "L. & A. Seragnoli", Site #959	Bologna		Italy	40138
113	A.O. Universitaria Policlinico Vittorio Emanuele di Catania, Site #530	Catania		Italy	95124
114	Clinica Ematologica, Site #528	Genova		Italy	16132
115	Ospedale Niguarda Ca' Granda di Milano, Site #531	Milan		Italy	20162
116	S.C. Ematologia, Site #960	Modena		Italy	41124
117	San Gerardo Hospital, Site #961	Monza		Italy	20900
118	U.O.C Ematologia con trapianto di midollo osseo, Site #560	Napoli		Italy	80131
119	Universita Federico II, Site #510	Napoli		Italy
120	SCDU Medicina Interna II - Indirizzo Ematologico, Site #785	Orbassano		Italy	10043
121	Dipartimento di Biotecnologie Cellulari ed Ematologia Universita La Sapienza - Policlinico Umberto I, Site #511	Rome		Italy	00161
122	U.O. di Ematologia - Ospedale S. Eugenio, Site #962	Rome		Italy	144
123	The Catholic University of Korea, Site #938	Seocho-gu	Seoul	Korea, Republic of	137-701
124	VU Medical Centre - Department Haematology, Site #948	Amsterdam		Netherlands	1081-HV
125	Auckland City Hospital, Site #921	Grafton	Auckland	New Zealand	1023
126	Christchurch Hospital, Site #922	Christchurch		New Zealand
127	Waikato Hospital, Site #977	Hamilton		New Zealand
128	North Shore Hospital, Site #976	Takapuna		New Zealand	0740
129	Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Medyczne, Site #548	Gdansk		Poland
130	Malopolskie Centrum Medyczne, Site #546	Krakow		Poland
131	Klinika Hematologii Wojewodzkiego Szpitala Specjalistycznego, Site #550	Lodz		Poland
132	Oddzial Hematologii, Site #551	Rzeszow		Poland	35-055
133	Katedra i Klinika Hematologii, Site #547	Wroclaw		Poland
134	Instituto Portugues de Oncologia, Site #545	Lisboa		Portugal	1099-023
135	Fundacion de Investigacion de Diego, Site #199	San Juan		Puerto Rico	00927
136	Singapore General Hospital, Site #939	Singapore		Singapore
137	Narodny onkologicky ustav, Site #532	Bratislava		Slovakia	833 10
138	Univerzitna nemocnica Martin, Site #533	Martin		Slovakia	036 59
139	Complejo Hospitalario Universitario A Coruna, Hospital "Teresa Herrera," Site #554	A Coruna		Spain	15006
140	Hospital Universitari Germans Trias i Pujol, Site #512	Badalona		Spain	08916
141	Hospital Clinic, Site #963	Barcelona		Spain	08036
142	Institut Catala d' Oncologia de Girona, S. de Hematologia Clinica, Site #734	Girona		Spain	17007
143	Hospital Universitari Son Espases, Site #553	Islas Baleares		Spain	07010
144	Hospital Universitario La Princesa, Site #555	Madrid		Spain	28006
145	Hospital Gregorio Maranon, Site #536	Madrid		Spain	28007
146	H.U. Ramon y Cajal, Site #538	Madrid		Spain	28034
147	Hospital Universitario 12 de Octubre, Site #537	Madrid		Spain	28041
148	Hospital La Paz, Site #966	Madrid		Spain	28046
149	Hospital Universitario Central de Asturias, Site #535	Oviedo		Spain	33006
150	Hospital Universitario de Salamanca, Site #965	Salamanca		Spain	37007
151	Hospital Clinico Universitario de Valencia, Site #964	Valencia		Spain	46010
152	Skane University Hospital, Site #944	Lund		Sweden
153	Karolinska University Hospital Huddinge, Site #534	Stockholm		Sweden
154	Karolinska University Hospital Solna, Site #763	Stockholm		Sweden
155	Uppsala University Hospital, Site #945	Uppsala		Sweden
156	Kantonsspital Aarau, Site #541	Aarau		Switzerland	5001
157	Kantonsspital St. Gallen, Site #707	St Gallen		Switzerland	9007
158	Kaohsiung Chang Gung Memorial Hospital, Site #980	Kaohsiung		Taiwan
159	China Medical University Hospital, Site #978	Taiching		Taiwan	40447
160	National Taiwan University Hospital, Site #979	Taipei		Taiwan	10002
161	Western General Hospital, Site #556	Edinburgh		United Kingdom	EH4 2XU
162	Kent and Medway Cancer Research Network, Site #558	Gillingham		United Kingdom
163	University of Glasgow, Site #797	Glasgow		United Kingdom	G120SB
164	St. James University Hospital, Site #540	Leeds		United Kingdom	LS9 7TF
165	Royal Liverpool University Hospital, Site #969	Liverpool		United Kingdom	L7 8XP
166	Hammersmith Hospital, Site #967	London		United Kingdom
167	Newcastle University, Site #970	Newcastle		United Kingdom
168	Norfolk & Norwich University Hospital Foundation Trust, Site #557	Norwich		United Kingdom
169	Nottingham University Hospitals NHS Trust, Site #968	Nottingham		United Kingdom	NG5 1PB
170	Oxford University Hospitals NHS Trust, Site #543	Oxford		United Kingdom

Sponsors and Collaborators

• Ariad Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ariad Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01650805
• Other Study ID Numbers: AP24534-12-301
• First Posted: Jul 26, 2012
• Last Update Posted: Nov 17, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Ariad Pharmaceuticals: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate; Ponatinib

Study Results

Participant Flow

Pre-assignment Detail	A total of 307 subjects were enrolled (ponatinib patients: 155; imatinib patients: 152). Patients were randomized in a 1:1 fashion to receive either ponatinib or imatinib.

Arm/Group Title	Ponatinib	Imatinib
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily	imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Period Title: Overall Study
STARTED	155	152
COMPLETED	154	152
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Ponatinib	Imatinib	Total
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily	imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily	Total of all reporting groups
Overall Participants	155	152	307
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	119 76.8%	116 76.3%	235 76.5%
>=65 years	36 23.2%	36 23.7%	72 23.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (15.66)	51.2 (15.19)	51.5 (15.41)
Sex: Female, Male (Count of Participants)
Female	58 37.4%	60 39.5%	118 38.4%
Male	97 62.6%	92 60.5%	189 61.6%
Region of Enrollment (participants) [Number]
Portugal	0 0%	2 1.3%	2 0.7%
United States	48 31%	34 22.4%	82 26.7%
Hong Kong	4 2.6%	1 0.7%	5 1.6%
Taiwan	3 1.9%	2 1.3%	5 1.6%
Finland	1 0.6%	0 0%	1 0.3%
Spain	16 10.3%	9 5.9%	25 8.1%
Italy	15 9.7%	14 9.2%	29 9.4%
United Kingdom	6 3.9%	12 7.9%	18 5.9%
France	14 9%	21 13.8%	35 11.4%
Czech Republic	1 0.6%	3 2%	4 1.3%
Canada	16 10.3%	13 8.6%	29 9.4%
Poland	0 0%	1 0.7%	1 0.3%
Belgium	3 1.9%	2 1.3%	5 1.6%
Singapore	1 0.6%	11 7.2%	12 3.9%
Australia	1 0.6%	6 3.9%	7 2.3%
Netherlands	1 0.6%	1 0.7%	2 0.7%
Germany	11 7.1%	12 7.9%	23 7.5%
New Zealand	4 2.6%	4 2.6%	8 2.6%
Sweden	6 3.9%	2 1.3%	8 2.6%
Korea, Republic of	3 1.9%	2 1.3%	5 1.6%
Switzerland	1 0.6%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Major Molecular Response (MMR) Rate at 12 Months
Description	A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.
Time Frame	12 months after first dose

Outcome Measure Data

Analysis Population Description

Patients with 12 month assessment (due to early termination of the study, none of the endpoints could be evaluated as planned).

Arm/Group Title	Ponatinib	Imatinib
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily	imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Measure Participants	10	13
Number [participants]	8 5.2%	5 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ponatinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified Analysis by Sokal score

2. Secondary Outcome

Title	MMR Rate
Description	To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years
Time Frame	5 years after first dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	<10% BCR-ABL^IS Rate
Description	To compare the proportion of patients achieving a ratio of <10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (<10% BCR-ABL^IS), in patients administered ponatinib versus those administered imatinib
Time Frame	3 months after first dose

Outcome Measure Data

Analysis Population Description

Patients with 3 month assessment

Arm/Group Title	Ponatinib	Imatinib
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily	imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Measure Participants	109	114
Number [participants]	103 66.5%	77 50.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ponatinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified Analysis by Sokal score

4. Secondary Outcome

Title	Complete Cytogenetic Response (CCyR) Rate
Description	The percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. Responses are defined as follows: Complete (CCyR): 0% Ph+ metaphases.
Time Frame	12 months after first dose

Outcome Measure Data

Analysis Population Description

Patients with 12 month assessment

Arm/Group Title	Ponatinib	Imatinib
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily	imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
Measure Participants	5	7
Number [participants]	5 3.2%	6 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ponatinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.317
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified Analysis by Sokal score

5. Secondary Outcome

Title	Progression-free Survival
Description	To compare, according to treatment with ponatinib versus imatinib, progression-free survival
Time Frame	Up to 8 years after the last patient's first dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival
Description	To compare, according to treatment with ponatinib versus imatinib, overall survival
Time Frame	Up to 8 years after the last patient's first dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Patients were followed-up for AEs from the time of informed consent until 30 days after the close of the trial. The median follow-up was 4.97 months (range: 0.03, 17.57) for ponatinib patients, and 5.32 months (range: 0.49, 14.05) for imatinib patients.
Arm/Group Title	Ponatinib 45 mg		Imatinib 400 mg
Arm/Group Description	ponatinib: 45 mg tablet, taken orally once daily		imatinib (Gleevec/ Glivec): 400 mg tablet, taken orally once daily
All Cause Mortality
	Ponatinib 45 mg		Imatinib 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ponatinib 45 mg		Imatinib 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/154 (31.8%)		13/152 (8.6%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	2/154 (1.3%)	2	0/152 (0%)	0
ANGINA PECTORIS	2/154 (1.3%)	2	0/152 (0%)	0
ATRIAL FIBRILLATION	3/154 (1.9%)	3	0/152 (0%)	0
CARDIAC ARREST	0/154 (0%)	0	1/152 (0.7%)	1
CARDIAC FAILURE	2/154 (1.3%)	4	0/152 (0%)	0
CORONARY ARTERY DISEASE	1/154 (0.6%)	1	0/152 (0%)	0
MYOPERICARDITIS	1/154 (0.6%)	1	0/152 (0%)	0
PERICARDIAL EFFUSION	1/154 (0.6%)	1	0/152 (0%)	0
Ear and labyrinth disorders
VERTIGO POSITIONAL	1/154 (0.6%)	1	1/152 (0.7%)	1
Eye disorders
EYE PAIN	1/154 (0.6%)	1	0/152 (0%)	0
PHOTOPHOBIA	1/154 (0.6%)	1	0/152 (0%)	0
RETINAL VEIN THROMBOSIS	1/154 (0.6%)	1	0/152 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	2/154 (1.3%)	3	0/152 (0%)	0
NAUSEA	1/154 (0.6%)	1	0/152 (0%)	0
PANCREATITIS	5/154 (3.2%)	5	0/152 (0%)	0
SMALL INTESTINAL OBSTRUCTION	1/154 (0.6%)	1	0/152 (0%)	0
VOMITING	1/154 (0.6%)	1	0/152 (0%)	0
General disorders
NON-CARDIAC CHEST PAIN	1/154 (0.6%)	1	0/152 (0%)	0
OEDEMA PERIPHERAL	0/154 (0%)	0	1/152 (0.7%)	2
PYREXIA	2/154 (1.3%)	2	1/152 (0.7%)	1
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	1/154 (0.6%)	1	0/152 (0%)	0
Hepatobiliary disorders
CHOLECYSTITIS	1/154 (0.6%)	1	0/152 (0%)	0
HEPATITIS	0/154 (0%)	0	1/152 (0.7%)	1
Infections and infestations
BACTERIAL PYELONEPHRITIS	1/154 (0.6%)	1	0/152 (0%)	0
CERVICITIS	1/154 (0.6%)	1	0/152 (0%)	0
DISSEMINATED TUBERCULOSIS	1/154 (0.6%)	1	0/152 (0%)	0
DIVERTICULITIS	1/154 (0.6%)	1	0/152 (0%)	0
HEPATITIS B	0/154 (0%)	0	1/152 (0.7%)	1
HERPES ZOSTER	0/154 (0%)	0	1/152 (0.7%)	1
LUNG INFECTION	0/154 (0%)	0	1/152 (0.7%)	1
PARAINFLUENZAE VIRUS INFECTION	1/154 (0.6%)	1	0/152 (0%)	0
PARASPINAL ABSCESS	0/154 (0%)	0	1/152 (0.7%)	1
PERICOLIC ABSCESS	1/154 (0.6%)	1	0/152 (0%)	0
PNEUMONIA	2/154 (1.3%)	3	1/152 (0.7%)	1
PYELONEPHRITIS	1/154 (0.6%)	1	0/152 (0%)	0
RESPIRATORY TRACT INFECTION	1/154 (0.6%)	1	0/152 (0%)	0
SEPSIS	1/154 (0.6%)	1	0/152 (0%)	0
VESTIBULAR NEURONITIS	1/154 (0.6%)	1	0/152 (0%)	0
VIRAL UPPER RESPIRATORY TRACT INFECTION	0/154 (0%)	0	1/152 (0.7%)	1
Injury, poisoning and procedural complications
COMPRESSION FRACTURE	1/154 (0.6%)	1	0/152 (0%)	0
PERIORBITAL CONTUSION	1/154 (0.6%)	1	0/152 (0%)	0
SPLENIC RUPTURE	0/154 (0%)	0	1/152 (0.7%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/154 (0.6%)	1	0/152 (0%)	0
AMYLASE INCREASED	1/154 (0.6%)	1	0/152 (0%)	0
C-REACTIVE PROTEIN INCREASED	1/154 (0.6%)	1	0/152 (0%)	0
PLATELET COUNT DECREASED	3/154 (1.9%)	3	0/152 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	0/154 (0%)	0	1/152 (0.7%)	1
FAILURE TO THRIVE	1/154 (0.6%)	1	0/152 (0%)	0
HYPONATRAEMIA	1/154 (0.6%)	1	0/152 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	1/154 (0.6%)	1	0/152 (0%)	0
BONE PAIN	0/154 (0%)	0	1/152 (0.7%)	1
MUSCULOSKELETAL CHEST PAIN	0/154 (0%)	0	1/152 (0.7%)	1
NECK PAIN	1/154 (0.6%)	1	0/152 (0%)	0
POLYARTHRITIS	1/154 (0.6%)	1	0/152 (0%)	0
SACROILIITIS	1/154 (0.6%)	1	0/152 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ANGIOMYOLIPOMA	1/154 (0.6%)	1	0/152 (0%)	0
BLAST CRISIS IN MYELOGENOUS LEUKAEMIA	0/154 (0%)	0	2/152 (1.3%)	2
CHLOROMA	0/154 (0%)	0	1/152 (0.7%)	1
CLEAR CELL RENAL CELL CARCINOMA	0/154 (0%)	0	1/152 (0.7%)	1
Nervous system disorders
CEREBROVASCULAR ACCIDENT	1/154 (0.6%)	1	0/152 (0%)	0
DYSARTHRIA	1/154 (0.6%)	1	0/152 (0%)	0
HEADACHE	1/154 (0.6%)	1	0/152 (0%)	0
HYPOXIC-ISCHAEMIC ENCEPHALOPATHY	0/154 (0%)	0	1/152 (0.7%)	1
LOSS OF CONSCIOUSNESS	1/154 (0.6%)	1	0/152 (0%)	0
POLYNEUROPATHY	1/154 (0.6%)	1	0/152 (0%)	0
PRESYNCOPE	0/154 (0%)	0	1/152 (0.7%)	1
RADICULITIS CERVICAL	1/154 (0.6%)	1	0/152 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/154 (0.6%)	1	0/152 (0%)	0
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	1/154 (0.6%)	1	0/152 (0%)	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/154 (0.6%)	1	0/152 (0%)	0
PLEURAL EFFUSION	0/154 (0%)	0	2/152 (1.3%)	2
PULMONARY OEDEMA	0/154 (0%)	0	1/152 (0.7%)	1
RESPIRATORY FAILURE	1/154 (0.6%)	1	0/152 (0%)	0
Vascular disorders
HYPERTENSION	1/154 (0.6%)	1	0/152 (0%)	0
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	2/154 (1.3%)	2	0/152 (0%)	0
PERIPHERAL ARTERY THROMBOSIS	1/154 (0.6%)	1	0/152 (0%)	0
Other (Not Including Serious) Adverse Events
	Ponatinib 45 mg		Imatinib 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/154 (94.2%)		144/152 (94.7%)
Blood and lymphatic system disorders
ANAEMIA	13/154 (8.4%)	15	12/152 (7.9%)	14
Eye disorders
DRY EYE	10/154 (6.5%)	10	3/152 (2%)	3
EYELID OEDEMA	1/154 (0.6%)	1	13/152 (8.6%)	13
PERIORBITAL OEDEMA	1/154 (0.6%)	1	33/152 (21.7%)	37
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	10/154 (6.5%)	11	5/152 (3.3%)	5
ABDOMINAL PAIN	54/154 (35.1%)	69	15/152 (9.9%)	15
CONSTIPATION	41/154 (26.6%)	48	3/152 (2%)	3
DIARRHOEA	20/154 (13%)	28	41/152 (27%)	54
DRY MOUTH	11/154 (7.1%)	11	5/152 (3.3%)	5
DYSPEPSIA	7/154 (4.5%)	7	9/152 (5.9%)	10
NAUSEA	34/154 (22.1%)	44	52/152 (34.2%)	58
VOMITING	17/154 (11%)	18	28/152 (18.4%)	30
General disorders
ASTHENIA	6/154 (3.9%)	6	12/152 (7.9%)	14
CHILLS	10/154 (6.5%)	12	6/152 (3.9%)	6
FATIGUE	32/154 (20.8%)	37	30/152 (19.7%)	35
OEDEMA PERIPHERAL	14/154 (9.1%)	15	22/152 (14.5%)	24
PAIN	9/154 (5.8%)	10	2/152 (1.3%)	2
PYREXIA	26/154 (16.9%)	31	6/152 (3.9%)	8
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	5/154 (3.2%)	5	13/152 (8.6%)	16
Investigations
ALANINE AMINOTRANSFERASE INCREASED	20/154 (13%)	29	2/152 (1.3%)	3
AMYLASE INCREASED	14/154 (9.1%)	20	1/152 (0.7%)	1
ASPARTATE AMINOTRANSFERASE INCREASED	18/154 (11.7%)	24	6/152 (3.9%)	7
BLOOD ALKALINE PHOSPHATASE INCREASED	14/154 (9.1%)	20	5/152 (3.3%)	5
LIPASE INCREASED	41/154 (26.6%)	68	11/152 (7.2%)	13
NEUTROPHIL COUNT DECREASED	8/154 (5.2%)	15	17/152 (11.2%)	34
PLATELET COUNT DECREASED	36/154 (23.4%)	65	21/152 (13.8%)	37
WEIGHT DECREASED	9/154 (5.8%)	11	2/152 (1.3%)	2
WHITE BLOOD CELL COUNT DECREASED	5/154 (3.2%)	5	9/152 (5.9%)	11
Metabolism and nutrition disorders
DECREASED APPETITE	18/154 (11.7%)	20	7/152 (4.6%)	8
HYPERTRIGLYCERIDAEMIA	13/154 (8.4%)	14	7/152 (4.6%)	8
Musculoskeletal and connective tissue disorders
ARTHRALGIA	29/154 (18.8%)	33	23/152 (15.1%)	29
BACK PAIN	11/154 (7.1%)	13	6/152 (3.9%)	7
BONE PAIN	13/154 (8.4%)	19	12/152 (7.9%)	16
MUSCLE SPASMS	11/154 (7.1%)	12	52/152 (34.2%)	62
MUSCULOSKELETAL PAIN	10/154 (6.5%)	11	4/152 (2.6%)	4
MYALGIA	40/154 (26%)	44	27/152 (17.8%)	31
PAIN IN EXTREMITY	19/154 (12.3%)	19	12/152 (7.9%)	15
Nervous system disorders
DIZZINESS	15/154 (9.7%)	21	9/152 (5.9%)	11
HEADACHE	50/154 (32.5%)	61	20/152 (13.2%)	27
LETHARGY	3/154 (1.9%)	3	10/152 (6.6%)	12
Psychiatric disorders
ANXIETY	8/154 (5.2%)	8	5/152 (3.3%)	5
DEPRESSION	8/154 (5.2%)	8	5/152 (3.3%)	5
INSOMNIA	16/154 (10.4%)	17	4/152 (2.6%)	4
Respiratory, thoracic and mediastinal disorders
COUGH	8/154 (5.2%)	9	8/152 (5.3%)	8
DYSPNOEA	13/154 (8.4%)	18	5/152 (3.3%)	5
OROPHARYNGEAL PAIN	10/154 (6.5%)	10	3/152 (2%)	3
Skin and subcutaneous tissue disorders
ALOPECIA	17/154 (11%)	17	8/152 (5.3%)	8
DRY SKIN	27/154 (17.5%)	29	5/152 (3.3%)	5
ERYTHEMA	11/154 (7.1%)	12	2/152 (1.3%)	3
NIGHT SWEATS	7/154 (4.5%)	7	9/152 (5.9%)	10
PRURITUS	18/154 (11.7%)	20	11/152 (7.2%)	15
RASH	58/154 (37.7%)	100	25/152 (16.4%)	41
RASH PRURITIC	6/154 (3.9%)	8	11/152 (7.2%)	14
Vascular disorders
HYPERTENSION	27/154 (17.5%)	37	3/152 (2%)	4

Limitations/Caveats

Trial was discontinued early.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.