Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)

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ClinicalTrials.gov Identifier: NCT01570868

Recruitment Status : Terminated (Closed due to slow accrual)

First Posted : April 4, 2012

Results First Posted : September 6, 2019

Last Update Posted : May 1, 2024

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Sponsor:

Collaborator:

Ariad Pharmaceuticals

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Leukemia
Intervention	Drug: Ponatinib
Enrollment	51

Participant Flow

Recruitment Details	Recruitment period: April 27, 2012 to May 12, 2015. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Details	Study terminated early.


Arm/Group Title	Ponatinib 45 mg	Ponatinib 30 mg
Arm/Group Description	Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.
Arm/Group Description	Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.
Period Title: Overall Study
Started	43	8
Completed	0	0
Not Completed	43	8
Reason Not Completed
Adverse Event	8	1
FDA Recommendation	23	3
Physician Decision	10	4
Lost to Follow-up	1	0
Withdrawal by Subject	1	0

Baseline Characteristics

Arm/Group Title		Ponatinib 45 mg	Ponatinib 30 mg	Total
Arm/Group Description		Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.	Total of all reporting groups
Arm/Group Description		Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.	Total of all reporting groups
Overall Number of Baseline Participants		43	8	51
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	43 participants	8 participants	51 participants
		52 (21 to 74)	42 (31 to 65)	43 (21 to 74)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	43 participants	8 participants	51 participants
	Female	19 44.2%	5 62.5%	24 47.1%
	Male	24 55.8%	3 37.5%	27 52.9%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	43 participants	8 participants	51 participants
United States		43 100.0%	8 100.0%	51 100.0%

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Complete Cytogenetic Response (CCyR)
Description	Proportion of participants with previously-untreated accelerated phase...
Description	Proportion of participants with previously-untreated accelerated phase CML attaining complete cytogenetic response (CCyR) at 6 months of treatment with Ponatinib classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases). CCyR defined as Ph positive 0%.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ponatinib 45 mg	Ponatinib 30 mg
Arm/Group Description:	Ponatinib 45 mg orally, once daily....	Ponatinib 30mg orally, once daily. ...
Arm/Group Description:	Ponatinib 45 mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.	Ponatinib 30mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.
Overall Number of Participants Analyzed	42	8
Measure Type: Count of Participants Unit of Measure: Participants
	40 95.2%	3 37.5%

2.Primary Outcome


Title	Number of Participants With Complete Cytogenetic Response (CCyR)
Description	Proportion of participants with previously-untreated accelerated phase...
Description	Proportion of participants with previously-untreated accelerated phase CML receiving treatment of Ponatinib achieving a Complete cytogenetic response (CCyR). Classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases. CCyR is defined as Ph positive 0%.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Ponatinib 45 mg	Ponatinib 30 mg
Arm/Group Description:	Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.
Arm/Group Description:	Ponatinib 45 mg orally, once daily.	Ponatinib 30 mg orally, once daily.
Overall Number of Participants Analyzed	42	8
Measure Type: Count of Participants Unit of Measure: Participants
	42 100.0%	6 75.0%

3.Secondary Outcome


Title	Toxicity Profile: Most Common Grade 3-4 Non-Hematologic Adverse Events (AEs) Seen in More Than 1 Participant
Description	Time to toxicity monitoring defined as any grade 3 or 4 drug-related n...
Description	Time to toxicity monitoring defined as any grade 3 or 4 drug-related non-hematologic adverse event that has not resolved to grade 2 or less after 6 weeks of optimal therapeutic management, or drug-related toxicity of any grade that in the opinion of the investigator prevents further therapy with ponatinib. Time to toxicity monitored using the Bayesian method of Thall, et al.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

One participant was not included in analysis.


Arm/Group Title	Ponatinib 45 mg	Ponatinib 30 mg
Arm/Group Description:	Ponatinib oral dose 45 mg daily.	Ponatinib oral dose 30 mg daily.
Arm/Group Description:	Ponatinib oral dose 45 mg daily.	Ponatinib oral dose 30 mg daily.
Overall Number of Participants Analyzed	43	8
Measure Type: Count of Participants Unit of Measure: Participants
Elevated Amylase	2 4.7%	0 0.0%
Lipase Elevation	15 34.9%	1 12.5%
Pancreatitis	7 16.3%	2 25.0%
Abdominal Pain	1 2.3%	0 0.0%
Hypertension	3 7.0%	0 0.0%
Elevated alanine aminotransferase (ALT)	2 4.7%	0 0.0%

Adverse Events

Time Frame	Adverse event collection minimally every 4 weeks for total duration of therapy up to one year, study collection period to be 3 to 5 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Ponatinib 45 mg		Ponatinib 30 mg
Arm/Group Description	Ponatinib 45 mg orally, once daily.		Ponatinib 30 mg orally, once daily.
Arm/Group Description	Ponatinib 45 mg orally, once daily.		Ponatinib 30 mg orally, once daily.
All-Cause Mortality
	Ponatinib 45 mg		Ponatinib 30 mg
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Ponatinib 45 mg		Ponatinib 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/43 (39.53%)		3/8 (37.50%)
Blood and lymphatic system disorders
Anemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Febrile neutropenia ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Cardiac disorders
Acute Coronary Syndrome ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Chest Pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Myocardial infarction ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Gastrointestinal disorders
abdominal pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Colitis ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Diarrhea ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Pancreatitis ^† 1	7/43 (16.28%)	10	2/8 (25.00%)	2
General disorders
Fever ^† 1	1/43 (2.33%)	2	0/8 (0.00%)	0
Non-Cardiac chest pain ^† 1	1/43 (2.33%)	2	0/8 (0.00%)	0
Infections and infestations
Infections and infestations-Other ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Lung Infection ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Pelvic infection ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Surgical and medical procedures - Other, Hysterectomy ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Urinary tract infection ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Metabolism and nutrition disorders
Hyperglycemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Hypoglycemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Nervous system disorders
Seizure ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Stroke ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Transient ischemic attacks ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Vascular disorders
Hypertension ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Vaso-Occulusive diasease ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Bialteral superfical femoral artery occulsion ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Peripheral vascular disease ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (4.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ponatinib 45 mg		Ponatinib 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/43 (81.40%)		6/8 (75.00%)
Blood and lymphatic system disorders
Anemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Febrile neutropenia ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Cardiac disorders
Acute Coronary Syndrome ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Cardiac Disorders other ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Chest Pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Myocardial Infarction ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Ear and labyrinth disorders
Tinnitus ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Endocrine disorders
Endocrine disorders ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Hypothyroidism ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Eye disorders
Dry eye ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Colitis ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Diarrhea ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Dyspepsia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Pancreatitis ^† 1	7/43 (16.28%)	7	2/8 (25.00%)	2
Pelvic infection ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
General disorders
Fever ^† 1	2/43 (4.65%)	3	0/8 (0.00%)	0
Non-cardiac chest pain ^† 1	1/43 (2.33%)	2	0/8 (0.00%)	0
Pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Infections and infestations
Infection other ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Urinary tract infection ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Injury, poisoning and procedural complications
Fracture ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Injury, poisoning and procedural complications ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Investigations
Increased Alanine aminotransferase ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Increased amylase ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Increased Aspartate aminotransferase ^† 1	1/43 (2.33%)	2	0/8 (0.00%)	0
Increased GGT ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Increased Lipase ^† 1	10/43 (23.26%)	15	1/8 (12.50%)	1
Weight gain ^† 1	3/43 (6.98%)	3	1/8 (12.50%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Hyperglycemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Hypoglycemia ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Musculoskeletal and connective tissue disorders
Bone pain ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
decreased range of motion, joint ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Musculoskeletal and connective tissue disorder ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Nervous system disorders
Cognitive disturbance ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Dysesthesia ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Memory impairment ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Nervous system disorders ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Peripheral sensory neuropathy ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Stroke ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Transient ischemic attacks ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Psychiatric disorders
Anxiety ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Decreased libido ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Depression ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Renal and urinary disorders
Acute Kidney Injury ^† 1	0/43 (0.00%)	0	1/8 (12.50%)	1
Renal and urinary disorders ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Reproductive system and breast disorders
Reproductive system and breast disorders ^† 1	2/43 (4.65%)	2	1/8 (12.50%)	1
Respiratory, thoracic and mediastinal disorders
Lung infection ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Skin and subcutaneous tissue disorders
Dry Skin ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Erythroderma ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Skin and subcutaneous tissue disorder ^† 1	2/43 (4.65%)	2	0/8 (0.00%)	0
Skin hyperpigmentation ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Rash Acneiform ^† 1	1/43 (2.33%)	1	0/8 (0.00%)	0
Surgical and medical procedures
Surgical and medical procedures ^† 1	5/43 (11.63%)	5	0/8 (0.00%)	0
Vascular disorders
Hypertension ^† 1	3/43 (6.98%)	3	0/8 (0.00%)	0
Vascular disorders ^† 1	3/43 (6.98%)	3	0/8 (0.00%)	0
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (4.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Jorge Cortes, MD/Professor, Leukemia
Organization:	The University of Texas (UT) MD Anderson Cancer Center
Phone:	713-792-7734
EMail:	CR_Study_Registration@mdanderson.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jain P, Kantarjian H, Boddu PC, Nogueras-Gonzalez GM, Verstovsek S, Garcia-Manero G, Borthakur G, Sasaki K, Kadia TM, Sam P, Ahaneku H, O'Brien S, Estrov Z, Ravandi F, Jabbour E, Cortes JE. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019 Mar 26;3(6):851-861. doi: 10.1182/bloodadvances.2018025874.

Issa GC, Kantarjian HM, Gonzalez GN, Borthakur G, Tang G, Wierda W, Sasaki K, Short NJ, Ravandi F, Kadia T, Patel K, Luthra R, Ferrajoli A, Garcia-Manero G, Rios MB, Dellasala S, Jabbour E, Cortes JE. Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment. Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.

Jain P, Kantarjian H, Jabbour E, Gonzalez GN, Borthakur G, Pemmaraju N, Daver N, Gachimova E, Ferrajoli A, Kornblau S, Ravandi F, O'Brien S, Cortes J. Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study. Lancet Haematol. 2015 Sep;2(9):e376-83. doi: 10.1016/S2352-3026(15)00127-1.

Layout table for additonal information

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01570868
Other Study ID Numbers:	2012-0074 NCI-2012-00572 ( Registry Identifier: NCI CTRP )
First Submitted:	April 2, 2012
First Posted:	April 4, 2012
Results First Submitted:	May 26, 2017
Results First Posted:	September 6, 2019
Last Update Posted:	May 1, 2024

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