Management of Transformed Chronic myeloid leukaemia: Ponatinib and Intensive chemotherapy
| ISRCTN | ISRCTN98986889 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98986889 |
| EudraCT/CTIS number | 2012-005629-65 |
| Secondary identifying numbers | 15879 |
- Submission date
- 05/03/2014
- Registration date
- 05/03/2014
- Last edited
- 16/12/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Prof Mhairi Copland
Scientific
Scientific
MATCHPOINT Trial Office
Cancer Research UK Clinical Trials Unit
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B154 2TH
United Kingdom
| Matchpoint@trials.bham.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please contact your consultant or research nurse for a patient information sheet |
| Scientific title | Management of Transformed Chronic myeloid leukaemia: Ponatinib and Intensive chemotherapy: a dose finding trial |
| Study 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(s) | NRES Committee South Central - Berkshire B, 11/12/2013, ref.13/SC/0583 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 15/03/2014 |
| Overall study end date | 26/04/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Total final enrolment | 17 |
| 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 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
- England
- United Kingdom
Study participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
B15 2TT
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Industry
Incyte Corporation
No information available
Bloodwise
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 10/12/2021 | 16/12/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
16/12/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
01/11/2018: The following changes were made to the trial record:
1. Contact details updated.
2. The funder names changed from Ariad Pharmaceuticals to Incyte Corporation and from Leukaemia and Lymphoma Research to Bloodwise.
24/10/2018: Publication and dissemination plan and IPD sharing statement.
09/10/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 02/06/2017 to 26/04/2018.
2. The overall trial end date was changed from 15/09/2017 to 26/04/2021.
3. The intention to publish date was added.
