Study of Ponatinib (Iclusig) for Prevention of Relapse After Allogeneic Stem Cell Transplantation (allo-SCT) in FLT3-ITD AML Patients

NCT03690115 | Completed Phase 2 DMC

• 1 other identifier: P1701_ PONALLO
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 14

Brief Summary

Recent advances in acute myeloid leukemia (AML) have been characterized by a better understanding of disease biology. As such, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have been recognized as conferring a poor prognosis. The FLT3-ITD molecular mutation is observed in about one-quarter of patients diagnosed with AML. Patients presenting with this abnormality are referred for early allogeneic stem-cell transplantation (allo-SCT). However, some data suggest that FLT3-ITD remains associated with a poor prognosis even after allo-SCT because of higher risk of relapse and strategies for preventing relapse in the post-transplant setting are required (Hu et al, Expert Rev Hematol, 2014). For example, in a large cohort of patients (Brunet et al, JCO, 2012), the incidence of relapse for FLT3-ITD AML patients after allo-SCT was 30% at 2-years, significantly higher compared to FLT3-ITD negative patients (p=0.006). Ponatinib (Iclusig®) is an orally available, tyrosine kinase inhibitor with a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. Ponatinib also has in vitro inhibitory activity against a discrete set of kinases implicated in the pathogenesis of other hematologic malignancies, including FLT3, KIT, fibroblast growth factor receptor 1 (FGFR1), and platelet derived growth factor receptor α (PDGFRα). In vitro activity of ponatinib in AML has been already demonstrated (Gozgit et al, Mol Cancer Ther, 2011; Smith et al, Blood 2013). If some trials are on-going to test ponatinib alone or in combination with chemotherapy in FLT3-ITD AML (Clinical.trials.gov), no study is dedicated to the use of ponatinib in the post-transplant setting in order to prevent relapse in these patients. The main goal of this study will be to determine the maximal tolerated dose (MDT) of ponatinib after allo-SCT in FLT3-ITD AML patients, then to investigate the efficacy of ponatinib in a larger cohort of patients

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Relapse incidence at 2 years from transplant

  2 years

Secondary Outcomes (7)

• Overall survival

  2 years

• Leukemia free survival

  2 years

• Non-relapse mortality (NRM)

  day 100

• Acute and chronic GVHD

  2 years

• Influence of Ponatinib on Immune reconstitution PB lymphocyte cells

  1 years

Study Arms (1)

Experimental

EXPERIMENTAL

Administration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient

Drug: Ponatinib 30 MG

Interventions

Ponatinib 30 MG DRUG

Administration of ponatinib after allo-SCT transplant in FLT3-ITD AML patient

Experimental

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Engraftment
• Controlled GVHD
• Positive FLT-3 ITD AML in cytologic complete remission
• Have an Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Have adequate renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) for institution
• Have adequate hepatic function: Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome; Alanine aminotransferase (ALT) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present ; Aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic infiltration of the liver is present
• Have normal pancreatic status: Serum lipase and amylase ≤ 1.5 × ULN
• Have normal QTcF interval on screening electrocardiogram (ECG) evaluation,defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.
• Platelets ≥ 100 Giga/l; Neutrophils ≥ 1 Giga/l
• Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
• Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile).
• Provide written informed consent.
• Be willing and able to comply with scheduled visits and study procedures.

You may not qualify if:

• HIV positive, active Hepatitis B or C
• Childbearing or childbreast feeding women
• Women or men without effective contraceptive barrier if needed
• Previous myocardial infarction, or cerebral vascular accident, pancreatitis
• Respiratory insufficiency defined as DLCO \<40% of the corrected value
• Creatinine clearance ≤ 50ml/min
• Contra-indication to ponatinib
• Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Patients at high or very high risk of cardiovascular disease with any of the following
• Established cardiovascular disease Cardiac disease:
• Congestive heart failure greater than class II NYHA or
• Left ventricular ejection fraction (LVEF) \< 50% or
• Unstable angina (anginal symptoms at rest) or
• New onset angina (began within the last 3 months) or

Sponsors & Collaborators

• Versailles Hospital: lead

Study Sites (14)

CHU Angers

Angers, France

Location

CHu Brest

Brest, France

Location

CHU Caen

Caen, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, France

Location

CHU Grenoble

Grenoble, France

Location

CHU Lille

Lille, France

Location

CHU Limoges

Limoges, France

Location

Chevallier

Nantes, France

Location

Hopital St Antoine

Paris, France

Location

Hopital St Louis

Paris, France

Location

CHu Lyon

Pierre-Bénite, France

Location

CHU Poitiers

Poitiers, France

Location

CRLC Toulouse

Toulouse, France

Location

CHU Nancy

Vandœuvre-lès-Nancy, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: investigator coordinator

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: October 1, 2018
• Study Start: December 2, 2019
• Primary Completion: December 5, 2023
• Study Completion: December 31, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

FR (14)