Study to Evaluate the Reinduction and Second Stop of TKI with Ponatinib in CML in Molecular Response (ResToP)

NCT04160546 | Active Not Recruiting Phase 2

• 3 other identifiers: ResToP2018-003281-142023-508993-27-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of the present study is to determine the rate of successful treatment-free remission (TFR) within the first 52 weeks following cessation of ponatinib treatment in patients who achieved MR4. Eligible patients had been previously treated with TKI and when patients achieved an optimal molecular response, TKI treatment was discontinued. After loss of response, patients were treated again with a TKI treatment and have documented MR4 for one year at the time of switch to ponatinib to study entry. MR4 is defined as BCR-ABL transcript level ≤ 0.01% IS or undetectable BCR-ABL levels with sample sensitivity of at least 4 log.

Conditions

Chronic Myeloid Leukemia, Chronic Phase

Keywords

Chronic Myeloid Leukemia; Ponatinib

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a maintained MMR within 52 weeks following ponatinib Treatment-Free Remission (TFR)

  This variable is defined as the number of patients who have a maintained MMR and have not restarted TKI therapy in the first 52 weeks after starting ponatinib TFR phase divided by the number of patients who entered ponatinib TFR phase.

  52 weeks

Secondary Outcomes (9)

• Evaluate the toxicity and safety profile of 15 mg/24h dose treatment of ponatinib combined with ASA.

  104 weeks

• Evaluate thromboembolic events for study period.

  104 weeks

• Evaluate hemorrhagic events for study period.

  104 weeks

• Evaluate hemolytic events for study period.

  104 weeks

• Evaluate gastrointestinal events for study period.

  104 weeks

Other Outcomes (1)

• Evaluate the proportion of patients who achieve a MR 5 at ponatinib therapy cessation.

  104 weeks

Study Arms (1)

Ponatinib plus ASA treatment

EXPERIMENTAL

Patients will be treated with ponatinib 15 mg/day plus 100 mg/day ASA for 104 weeks. After that, ponatinib and ASA will be stopped.

Drug: Ponatinib 15 MG; Drug: Acetylsalicylic acid 100 MG

Interventions

Ponatinib 15 MG DRUG

Patients will receive ponatinib 15 mg/day for 104 weeks orally. Ponatinib will be self-administered by the patient on a daily schedule. Acetyl salicylic acid (ASA) (100 mg) will be used such auxiliary medicinal product in order to prevent vascular occlusive events related with ponatinib.

Ponatinib plus ASA treatment

Acetylsalicylic acid 100 MG DRUG

Patients will receive acetylsalicylic acid 100 mg/day for 104 weeks orally.

Ponatinib plus ASA treatment

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years of age.
• ECOG Performance Status of 0, 1, or 2.
• Patient with diagnosis of BCR-ABL positive and Ph+ CML-Chronic Phase.
• Patients who failed the first attempt of TKI discontinuation and after TKI reintroduction they achieve again MR4 and it is maintained and confirmed for more than one year.
• Patients who are able to take oral therapy
• Adequate end organ function as defined by:
• Direct bilirubin ≤ 1.5 x ULN except for i) patient 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),
• SGOT(AST) and SGPT(ALT) ≤ 2.5 x ULN,
• Serum lipase and amylase ≤ 1.5 x ULN,
• Alkaline phosphatase ≤ 2.5 x ULN,
• Serum creatinine ≤ 1.5 x ULN.
• Patients must have the following electrolyte values ≥ LLN limits or corrected to within normal limits with supplements prior to the first dose of study medication:
• Potassium,
• Magnesium,
• Total calcium (corrected for serum albumin)

You may not qualify if:

• Prior accelerate phase, blast crisis or autologous or allogenic transplant.
• Patients 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.
• CML 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).
• Are taking medications with a known risk of torsades de pointes (Annex 5).
• Patient ever attempted to permanently discontinue TKI treatment.
• Severe 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).
• 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 (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.
• 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.
• Have 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.
• Have a history of alcohol abuse.

Sponsors & Collaborators

• Fundacion CRIS de Investigación para Vencer el Cáncer: lead
• Incyte Biosciences UK: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (13)

Institut Català D'Oncologia L'Hospitalet (ICO)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Location

Institut Català d´oncologia Badalona (ICO)

Badalona, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Complejo Hospitalario Regional de Málaga

Málaga, Spain

Location

Hospital Virgen de La Victoria

Málaga, Spain

Location

Hospital General Universitario J.M. Morales Meseguer

Murcia, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

MeSH Terms

Conditions

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

Interventions

ponatinib; Aspirin

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

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Joaquín Martínez López, MD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Valentín García Gutierrez, MD

  Hospital Universitario Ramon y Cajal

  PRINCIPAL INVESTIGATOR

• Juan Carlos Hernández Boluda, MD

  Hospital Clínico de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 13, 2019
• Study Start: January 17, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (13)