Contact information
Type
Scientific
Primary contact
Prof Mhairi Copland
ORCID ID
Contact details
MATCHPOINT Trial Office
Cancer Research UK Clinical Trials Unit
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B154 2TH
United Kingdom
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Matchpoint@trials.bham.ac.uk
Additional identifiers
EudraCT number
2012-005629-65
ClinicalTrials.gov number
Protocol/serial number
15879
Study information
Scientific title
Management of Transformed Chronic myeloid leukaemia: Ponatinib and Intensive chemotherapy: a dose finding trial
Acronym
MATCHPOINT
Study hypothesis
The aim of this trial is to find a safe and effective dose of a drug called Ponatinib when used in combination with chemotherapy in patients with Chronic Myeloid Leukaemia (CML) whose disease has moved in to blast phase. Ponatinib is a Tyrosine Kinase Inhibitor (TKI). TKIs stop enzymes called Tyrosine Kinases from working. By stopping these enzymes from working the normal signals within the cells are disrupted. TKIs are often used in the treatment of cancers including leukaemias such as CML. 30 patients from the United Kingdom will be invited to take part in this trial.
Ethics approval
NRES Committee South Central - Berkshire B, 11/12/2013, ref.13/SC/0583
Study design
Non-randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please contact your consultant or research nurse for a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)
Intervention
12 lead ECG, 60 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Additional sub-study bloods, Additional OPTIONAL blood samples for sub study - 20 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Biochemistry, Biochemistry including renal and liver profile - 20 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Blood samples, Full blood count with differentials - 20 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Bone marrow evaluation, 60 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Buccal swab, And hair follicle for DNA if buccal swab insufficient to analyse (OPTIONAL); Chemotherapy (FLAGIDA), Chemotherapy (FLAGIDA) cycle administration as per local practice; Physical examination, 30 minutes, performed by Investigator or delegated qualified person at hospital/clinic; Ponatinib administration, Patient prescribed a bottle of tablets to last for each of the 48week cycles of trial treatment, followed by 3 monthly supplies of ponatinib on maintenance as long as the patient requires it.; Pregnancy test, 5 minutes, performed by Investigator or delegated qualified person at hospital/clinic
Follow Up Length: 36 month(s)
Study Entry: Registration only
Intervention type
Drug
Phase
Phase I/II
Drug names
Ponatinib
Primary outcome measure
Efficacy; Timepoint(s): Efficacy: Complete cytogenetic response (CCyR)
Secondary outcome measures
1. Incidence of Cytomegalovirus (CMV) reactivation rate and Graft Versus Host Disease (GVHD); Timepoint(s): post-transplant
2. Complete Cytogenetic Response (CCyR); Timepoint(s): within 2 cycles of treatment
3. Disease free survival (DFS); Timepoint(s): 3 year
4. Haematological response; Timepoint(s): within 2 cycles of treatment
5. Major Molecular Response (MMR); Timepoint(s): within 2 cycles of treatment
6. Overall survival (OS); Timepoint(s): 3 years
7. Relapse rate post allogeneic transplant or maintenance therapy; Timepoint(s): 1 and 3 year
8. Tolerability
9. Identification of the dose of ponatinib that can be safely delivered in combination
10. Toxicity profile of ponatinib + chemotherapy (FLAG-IDA); Timepoint(s): within 6 months or up to transplant (whichever time point arrives first). Toxicities will be measure; treatment related mortality; Timepoint(s): 1 and 3 year
Overall trial start date
15/03/2014
Overall trial end date
26/04/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
All of the following:
1. Ph positive or BCRABL positive CML in blastic transformation. Defined as one or more of the following being present: Blasts ≥30% in peripheral blood or bone marrow Extramedullary blast proliferation or large foci or clusters of blasts in the bone marrow biopsy
2. Age: ≥18
3. Suitable for intensive chemotherapy (FLAGIDA)
4. Adequate renal function defined as serum creatinine ≤1.5 X upper limit of normal (ULN)
5. Adequate liver function defined as: Total bilirubin < 1.5 X ULN Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN (< 5 X ULN if liver involvement with leukaemia)
6. Normal pancreatic status Lipase ≤ 1.5 X ULN and Amylase ≤ 1.5 X ULN
7. Normal QTcF interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in males or ≤470 ms in females.
8. Female and male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study until 30 days after the last dose of ponatinib.
9. Ability to comply with study procedures, in the Investigator's opinion.
10. Valid Informed Consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 30; UK Sample Size: 30
Participant exclusion criteria
1. Received chemotherapy other than hydroxycarbamide or anagrelide within 4 weeks of registration
2. Received therapy with a new TKI (i.e. changed TKI) following confirmation of blastic transformation up to two weeks of TKI therapy is allowed for those patients whose CML is in blastic phase at original diagnosis.
3. Previous treatment with intensive acute leukaemiastyle chemotherapy (FLAGIDA)
4. Prior allogeneic or autologous Stem Cell Transplant
5. Significant or active cardiovascular disease, specifically including but not restricted to:
Myocardial infarction within 6 months prior to registration
History of clinically significant atrial or ventricular arrhythmia
Unstable angina within 6 months prior to registration
Congestive heart failure within 6 months prior to registration
History of pancreatitis
6. Uncontrolled hypertriglyceridaemia (>450mg/dL)
7. Are pregnant or lactating
8. Underwent major surgery (with the exception of minor surgical procedures, such as catheter placement or Bone Marrow biopsy) within 14 days prior to registration
9. Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere
with the evaluation of the safety of the study treatment
Recruitment start date
02/12/2014
Recruitment end date
26/04/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
Funders
Funder type
Industry
Funder name
Incyte Corporation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Bloodwise
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/12/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list