Condition category
Cancer
Date applied
05/03/2014
Date assigned
05/03/2014
Last edited
02/07/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mrs Kathryn Wheeler

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
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.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=15879

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 measures

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

15/09/2017

Reason abandoned

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

02/06/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Ariad Pharmaceuticals

Alternative name(s)

Ariad

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Leukaemia and Lymphoma Research

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

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes