Display again
NCT02467270 | SNCTP000001885

Eine Studie zum Vergleich von drei Anfangsstärken von Ponatinib Tabletten bei Patienten mit resistenter chronischer myeloischer Leukämie in der chronischen Phase.

Data source: BASEC (Imported from 19.11.2019), WHO (Imported from 17.11.2019)
Changed: 21.07.2019
Disease category: Leukämie

Brief description of trial (Source of data: BASEC)

Es handelt sich um eine Studie die an mehreren Orten international durchgeführt wird. Die Teilnahme ist freiwillig. Patienten mit chronischer myeloischer Leukämie in der chronischen Phase (CP-CML) erhalten nach dem Zufallsprinzip eine von drei möglichen Dosen Ponatinib in Tablettenform.
Für die Studie kommen Patienten mit CP-CML in Frage, die mindestens zwei Tyrosinkinase-Inhibitoren (TKI) erhalten haben und nachweislich resistant gegen die Behandlung sind oder die eine bestimmte Mutation in der CML-Erbsubstanz haben.
In diese Studie werden ca. 276 Patientinnen/Patienten in mehr als 150 Prüfzentren weltweit eingeschlossen. Die Teilnahme an dieser Studie beträgt 24 Monate. Jeder Patient durchläuft vor der Behandlung eine bis zu 3-wöchige Phase in der Tests durchgeführt werden. Die Dauer der Einnahme von Ponatinib richtet sich nach danach, ob die Behandlung dem Patienten nutzt und danach, wie gut Ponatinib vertragen wird.
Zweck dieser Studie ist die Beurteilung verschiedener Stärken von Ponatinib, um festzustellen, welche Dosis die beste Kontrolle der Erkrankung bei geringstmöglichen Nebenwirkungen erzielt.
Gegenwärtig ist Ponatinib in einigen Ländern für den Verkauf zugelassen. Die Anfangsdosis in allen Ländern liegt bei 45 mg, das Medikament wird einmal pro Tag über den Mund eingenommen.
Aufgrund der Nebenwirkungen, die bei dieser Dosis auftreten, insbesondere der Verengung oder Verstopfung von Blutgefässen, die schwerwiegende Nebenwirkungen wie Herzinfarkt oder Schlaganfall zur Folge haben, wird untersucht, ob 45 mg die beste Anfangsdosis ist.

Health conditions investigated (Source of data: BASEC)

chronische myeloische Leukämie in der chronischen Phase

Health conditions (Source of data: WHO)

Myeloid Leukemia, Chronic, Chronic Phase

Rare disease (Source of data: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

zu prüfendes Medikament: Ponatinib Tabletten mit 45 mg, 30 mg oder 15 mg Wirkstoff einmal täglich zum Einnehmen

Interventions (Source of data: WHO)

Drug: Ponatinib 45 mg;Drug: Ponatinib 30 mg;Drug: Ponatinib 15 mg

Criteria for participation in trial (Source of data: BASEC)

erwachsene Patienten die an myeloischer Leukämie in der chronischen Phase erkrankt sind und die mindestens zwei Tyrosinkinase-Inhibitoren (TKI) erhalten haben und nachweislich resistant gegen die Behandlung sind oder die eine bestimmte Mutation in der CML-Erbsubstanz haben;
Blutwerte liegen innerhalb bestimmter Bereiche

Exclusion criteria (Source of data: BASEC)

medikamentöse Behandlung der myeloischen Leukämie innerhalb von vorhergehenden 14 Tagen, Stammzellentranslplantation innherhalb der 60 vorangegangenen Tage, Einnahme bestimmter Medikamente, bestimmte Erkrankungen (u.a. Herz-Kreislauf, Zentrales Nervensystem, unkontrollierter Diabetes), Schwangerschaft

Inclusion/Exclusion Criteria (Source of data: WHO)


Inclusion Criteria:

1. Have CP-CML and have received at least two prior TKI therapies and have demonstrated
resistance to treatment OR have documented history of presence of T315I mutation after
receiving any number of prior TKI.

o The diagnosis of chronic myeloid leukemia (CML) will be made using standard
hematopathologic and cytogenetic criteria; CP-CML will be defined by all of the
following: i <15% blasts in bone marrow ii <30% blasts plus promyelocytes in bone
marrow iii <20% basophils in peripheral blood. iv >= 100*10^9/liter (L) platelets
(>=100,000/mm^3). v No evidence of extramedullary disease except hepatosplenomegaly vi
No prior diagnosis of AP-CML, and BP-CML

o Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence
of the t(9;22) Philadelphia chromosome.

i Variant translocations are only allowed provided they meet inclusion criterion 1d.

o Resistance to prior TKI therapy is defined as follows (participants must meet at
least 1 criterion): i Three months after the initiation of prior TKI therapy: No
cytogenetic response (>95% Ph+) or failure to achieve CHR or new mutation ii Six
months after the initiation of prior TKI therapy: BCR-ABL1IS >10% and/or Ph+ >65% or
new mutation iii Twelve months after the initiation of prior TKI therapy: BCR ABL1IS
>10% and/or Ph+ >35% or new mutation iv At any time after the initiation of prior TKI
therapy, the development of a new BCR-ABL1 kinase domain mutation(s) v At any time
after the initiation of prior TKI therapy, the development of new clonal evolution vi
At any time after the initiation of prior TKI therapy, the loss of CHR, or CCyR, or
the confirmed loss of MMR in 2 consecutive tests, one of which has a BCR-ABL1IS
transcript level of >=1% or new mutation

o >1% of BCR-ABL1IS as shown by real-time polymerase chain reaction

2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

3. Have adequate renal function as defined by the following criterion:

- Serum creatinine <=1.5*ULN for institution

- Estimated creatinine clearance >=30 milliliter per minute (mL/min)
(Cockcroft-Gault formula)

4. Have adequate hepatic function as defined by the following criteria:

- Total serum bilirubin <=1.5*ULN, unless due to Gilbert's syndrome

- Alanine transaminase (ALT) <=2.5*ULN, or <=5*ULN if leukemic infiltration of the
liver is present

- Aspartate transaminase (AST) <=2.5*ULN, or <=5*ULN if leukemic infiltration of
the liver is present

5. Have normal pancreatic status as defined by the following criterion:

o Serum lipase and amylase <=1.5*ULN

6. Have normal QT interval corrected (Frederica) (QTcF) interval on screening
electrocardiogram (ECG) evaluation, defined as QTcF of <=450 milliseconds (ms) in
males or <=470 ms in females.

7. Have a negative pregnancy test documented prior to enrollment (for females of
childbearing potential).

8. Agree to use a highly effective form of contraception with sexual partners from
randomization through at least 4 months after the end of treatment (for female and
male participants who are fertile).

9. Provide written informed consent.

10. Be willing and able to comply with scheduled visits and study procedures.

11. Have recovered from toxicities related to prior anticancer therapy to National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 grade
<=1.

Exclusion Criteria:

1. Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives
of the agent, whichever is longer, prior to receiving study drug.

2. Received interferon, cytarabine, or immunotherapy within 14 days, or any other
cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior
to receiving the first dose of ponatinib, or have not recovered (>grade 1 by NCI
CTCAE, version 4.0) from AEs (except alopecia), due to agents previously administered.

3. Have undergone autologous or allogeneic stem cell transplant <60 days prior to
receiving the first dose of ponatinib; have any evidence of ongoing graft-versus-host
disease (GVHD) or GVHD requiring immunosuppressive therapy.

4. Are being considered for hematopoietic stem cell transplant (HSCT) within 6-12 months
of enrollment (note: ponatinib is not to be used as a bridge to HSCT in this trial).

5. Are taking medications with a known risk of Torsades de Pointes.

6. Have previously been treated with ponatinib.

7. Have active CNS disease as evidenced by cytology or pathology; in the absence of
clinical CNS disease, lumbar puncture is not required. History itself of CNS
involvement is not exclusionary if CNS has been cleared with a documented negative
lumbar puncture.

8. Have clinically significant, uncontrolled, or active cardiovascular disease,
specifically including, but not restricted to:

- Any history of myocardial infarction (MI), unstable angina, cerebrovascular
accident, or Transient Ischemic Attack (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

9. Have uncontrolled hypertension (that is, >150 and >90 for systolic blood pressure
(SBP) and diastolic blood pressure (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 medical
monitor.

10. Have poorly controlled diabetes defined as HbA1c values of >7.5%. Participants with
preexisting, well-controlled diabetes are not excluded.

11. Have a significant bleeding disorder unrelated to CML.

12. Have a history of alcohol abuse.

13. Have a history of either acute pancre

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02467270

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02467270

Further information on trial

Date trial registered

02.06.2015

Incorporation of the first participant

30.06.2015

Recruitment status

Active, not recruiting

Academic title (Source of data: WHO)

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Source of data: WHO)

Phase 2

Primary end point (Source of data: WHO)

Percentage of Participants with <=1% BCR-ABL1IS at Month 12

Secundary end point (Source of data: WHO)

Percentage of Participants With Major Molecular Response (MMR) at Months 12 and 24;Major Cytogenetic Response (MCyR) Rates by Month 12;Duration of MMR;Percentage of Participants with Adjusted Incidence Rates for Arterial Occlusive Events (AOEs) and Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs);Percentage of Participants With CCyR at Month 12;Percentage of Participants With Major Molecular Response (MMR), Molecular Response 4 (MR4) and Molecular Response (MR4.5);Percentage of Participants With Molecular Response 1 (MR1) at Month 3;Percentage of Participants With Complete hematologic Response (CHR) at Month 3;Percentage of Participants with AEs Leading to Discontinuation and Dose Reduction;Percentage of Participants with Dose Interruptions;Duration of Response (DOR) of <=1% BCR-ABL1 IS;DOR for MMR;DOR in Responders;Time to Response;Percentage of Participants With Progression to AP or BP CML;Progression-free Survival (PFS);Overall Survival (OS)

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Zürich

Countries (Source of data: WHO)

Argentina, Australia, Belgium, Canada, Chile, China, Czech Republic, Czechia, Denmark, Finland, France, Germany, Hong Kong, Italy, Japan, Korea, Norway, Poland, Portugal, Republic of, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Studienkoordinator Herr Murat Aykut
+41 44 255 9627
murat.aykut@usz.ch

Contact for general information (Source of data: WHO)

Medical Director Clinical Science
Takeda

Contact for scientific information (Source of data: WHO)

Medical Director Clinical Science
Takeda

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Ariad Pharmaceuticals

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2016-00291

Secondary ID (Source of data: WHO)

2014-001617-12;15/LO/1192;AP24534-14-203