Multicenter, Open-Label, Single Arm, Phase II Exploratory Study to Evaluate the Effect of a One-Year Consolidation Treatment with Ponatinib 15 mg on Treatment Free-Remission Rate in Patients with Philadelphia-Positive Chronic Myeloid Leukemia, who had previously Achieved a Deep Molecular Response with Imatinib

Phase 1

Active, not recruiting

• Conditions: Chronic myeloid leukemia in chronic phase (CML-CP) on imatinib treatment for a minimum of 4 years with confirmed stable deep molecular response (MR4) for a minimum of 12 months prior to enrolment and no prior accelerated phase/blast crisis (AP/BC) or stem cell transplant (SCT).; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-004565-27-ES
• Lead Sponsor: FUNDACIÓN TEÓFILO HERNANDO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-17
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

Patients must meet all of the following criteria to be eligible for the study:
1Male or female patients = 18 years of age.
2ECOG performance status of 0, 1, or 2.
3Patient with diagnosis of BCR-ABL positive CML-CP.
4Patient has received a minimum of 4 years of imatinib treatment, as unique TKI therapy.
5Patient has achieved MR4 during at least 12 months with imatinib treatment, and determined by PCR lab assessment at screening.
6Adequate end organ function as defined by:
a.Total bilirubin = 1.5 x ULN except for i) patients with documented Gilbert’s syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range),
b.SGOT(AST) and SGPT(ALT) = 2.5 x ULN (upper limit of normal),
c.Serum lipase and amylase = 1.5 x ULN,
d.Alkaline phosphatase = 2.5 x ULN,
e.Serum creatinine = 1.5 x ULN.
7Patients must have the following electrolyte values = LLN limits or corrected to within normal limits with supplements prior to the first dose of study medication:
a.Potassium,
b.Magnesium,
c.Total calcium (corrected for serum albumin),
8Patients must have normal marrow function as defined below:
a.Absolute neutrophil count (ANC) = 1.5 x 109/L,
b.Platelets = 100 x 109/L,
c.Hemoglobin > 9.0 g/dL
9Patients with preexisting, well-controlled, diabetes are not excluded.
10Have normal QTcF interval on screening ECG evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females.
11Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study. The use of highly effective contraception should continue for at least 14 days after the last dose of study treatment or until the last day of TFR or for the duration of a monthly cycle of oral contraception, whichever is longer.
12Be willing and able to comply with scheduled visits and study procedures.
13Written informed consent obtained prior to any screening procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients are not eligible for participation in the study if they meet any of the following exclusion criteria:
1Prior AP, BC or autologous or allogenic transplant.
2Patients with known atypical transcript. An atypical transcript is defined by the presence of any transcript in the absence of the major transcripts b3a2 (e14a2) and b2a2 (e13a2) or p210 protein.
3CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past).
4Are taking medications with a known risk of torsades de pointes (Appendix A)
5Patient ever attempted to permanently discontinue imatinib or ponatinib treatment.
6Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g., uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection).
7 Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
a. Any history of MI, unstable angina, cerebrovascular accident, or TIA,
b. Any history of peripheral vascular infarction, including visceral infarction,
c. Any revascularization procedure, including the placement of a stent,
d. Congestive heart failure (NYHA class III or IV) within 6 months prior to enrollment, or LVEF less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment,
e. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia,
f. Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment
8Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
9Have a history of alcohol abuse.
10History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis.
11Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
12Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer.
13Have a history of another malignancy, other than cervical cancer in situ or no metastatic basal cell or squamous cell carcinoma of the skin; the exception is if patients have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
14Have undergone surgery (with the exception of minor surgical procedures, such as catheter placement) within 14 days prior to first dose of ponatinib.
15Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1.
16Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. See Appendix B for a list of these medications. This list may not be comprehensive.
17Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. These herbal medicines may include Echi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified