Ponatinib Hydrochloride as Second Line Therapy in Treating Patients With Chronic Myeloid Leukemia in Chronic Phase Resistant or Intolerant to Imatinib Mesylate, Dasatinib, or Nilotinib

NCT01746836 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2012-0669NCI-2014-01911
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ponatinib hydrochloride works as second line therapy in treating patients with chronic myeloid leukemia in chronic phase that has not responded to initial treatment (first line) with imatinib mesylate, dasatinib, or nilotinib or cannot tolerate imatinib mesylate, dasatinib, or nilotinib. Ponatinib hydrochloride may stop or control the growth of cancer cells by blocking a protein needed for cell growth.

Conditions

Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (2)

• MCyR at 6 months (MCyR6)

  The method of Kaplan and Meier will be used to estimate the unadjusted distribution of duration of MCyR. An appropriate time-to-event regression model will be fit to the event time data to assess the effects of patient covariates on the event time variable, with the particular model determined by preliminary goodness-of-fit analyses. The distribution of MCyR6 will be tabulated and effects of baseline patient covariates on this variable will be assessed by logistic regression.

  At 6 months

• Time-to-toxicity defined as any grade 3 or 4 drug-related adverse event that is not responsive to standard therapeutic management and requires permanent treatment discontinuation

  Time-to-toxicity will be monitored using the Bayesian method of Thall, et al. The method of Kaplan and Meier will be used to estimate the unadjusted distribution of time to toxicity. An appropriate time-to-event regression model will be fit to the event time data to assess the effects of patient covariates on the event time variable, with the particular model determined by preliminary goodness-of-fit analyses.

  Up to 30 days post-treatment

Secondary Outcomes (4)

• Duration of MCyR

  Up to 24 months

• Time to transformation to accelerated phase CML

  Up to 5 years

• Time to transformation to blastic phase CML

  Up to 5 years

• MMR

  Up to 24 months

Study Arms (1)

Ponatinib hydrochloride

EXPERIMENTAL

Patients receive ponatinib hydrochloride PO QD. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Ponatinib Hydrochloride; Other: Quality-of-Life Assessment

Interventions

Laboratory Biomarker Analysis OTHER

Blood draws.

Ponatinib hydrochloride

Ponatinib Hydrochloride DRUG

Starting dose: 30 mg by mouth once a day.

Also known as: AP24534 HCl, Iclusig

Ponatinib hydrochloride

Quality-of-Life Assessment OTHER

Surveys completed.

Also known as: Quality of Life Assessment

Ponatinib hydrochloride

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Philadelphia chromosome (Ph)-positive (by cytogenetics or fluorescent in situ hybridization \[FISH\]) or breakpoint cluster region (BCR)-ABL-positive (by polymerase chain reaction \[PCR\]) CML in chronic phase.
• Participants should have demonstrated to have failure to therapy to one FDA-approved second-generation TKI (currently bosutinib, dasatinib, and nilotinib are approved as frontline therapy), defined as per European leukemiaNet (ELN)35 or National Comprehensive Cancer Network (NCCN) recommendations:
• Less than complete hematologic response (CHR) at or beyond 3 months
• No partial cytogenetic response at or beyond 3 months
• BCR-ABL1 ≥ 10% at or beyond 3 months
• BCR-ABL1 ≥ 1% at or beyond 6 months
• Loss of CCyR or development of mutations or other clonal chromosomal abnormalities at any time during TKI treatment
• Age \>18 years
• ECOG performance of 0-2.
• Adequate end organ function, defined as the following: total bilirubin ≤1.5x ULN (unless due to Gilbert syndrome, in which case it should be ≤3.0x ULN), SGPT ≤2.5x ULN, creatinine clearance (CrCL) ≥ 30 mL/min (Cockcroft-Gault formula).
• Participants must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
• Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized:
• Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential OR women who are surgically sterile.
• In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.

You may not qualify if:

• Prior therapy with other BCR-ABL-targeted TKIs except bosutinib, dasatinib or nilotinib. Participants with T315I mutations are eligible and will be analyzed separately.
• Active NYHA cardiac class 3-4 heart disease
• Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Any history of MI, unstable angina, cerebrovascular accident, or TIA
• Any history of peripheral vascular infarction, including visceral infarction
• Any revascularization procedure, including the placement of a stent
• Congestive heart failure (CHF) (New York Heart Association \[NYHA\] class III or IV) within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment
• History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia
• Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment
• Participants with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders.
• Have uncontrolled hypertension (i.e., \>150 and \>90 for SBP and DBP, respectively). Participants with hypertension should be under treatment at study entry to ensure blood pressure control. Those requiring 3 or more antihypertensive medications should be discussed with the PI.
• Have poorly controlled diabetes defined as HbA1c values of \> 7.5%. Participants with preexisting, well-controlled, diabetes are not excluded.
• Pregnant or breast-feeding women are excluded.
• Participants with history of pancreatitis within 1 year of study or history of chronic pancreatitis.
• Participants in accelerated or blast phase, or patients who have ever been documented to be in blast phase CML, are excluded.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ponatinib

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

Study Officials

• Elias Jabbour, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elias Jabbour, MD

CONTACT

(713) 792-4764; ejabbour@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2012
• First Posted: December 11, 2012
• Study Start: January 17, 2013
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (1)