ROMAZA: Phase I study of romidespin and azacitidine in acute myeloid leukaemia patients
| ISRCTN | ISRCTN69211255 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN69211255 |
| EudraCT/CTIS number | 2011-005023-40 |
| Secondary identifying numbers | 15082 |
- Submission date
- 27/09/2013
- Registration date
- 27/09/2013
- Last edited
- 18/06/2024
- 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 of protocol
Contact information
Mrs Nadira Jilani
Scientific
Scientific
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
| romaza@trials.bham.ac.uk |
Study information
| Study design | Non-randomised interventional and observational; Design type: Treatment, Cohort study |
|---|---|
| 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 use the contact details to request a patient information sheet |
| Scientific title | ROMAZA: Phase I trial of combination therapy with romidepsin and azacitidine in patients with newly diagnosed, relapsed or refractory acute myeloid leukaemia ineligible for conventional chemotherapy |
| Study acronym | ROMAZA |
| Study objectives | This is a phase I, multicentre, dose finding trial of the use of Romidepsin in combination with Azacitidine in patients with newly diagnosed, relapsed or refractory Acute Myeloid Leukaemia (AML). Primary objective: To determine the maximum tolerated dose (MTD) of Romidepsin in combination with Azacitidine. Secondary objectives: 1. To determine the tolerability and safety of Romidepsin in combination with Azacitidine. 2. To determine the clinical activity of combined Romidepsin and Azacitidine treatment in patients with high risk AML. |
| Ethics approval(s) | NRES Committee South Central Oxford C, First MREC approval date 08/05/2013, ref: 13/SC/0157 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid) |
| Intervention | Patients with newly diagnosed, relapsed or refractory AML who are ineligible for conventional chemotherapy will be recruited to this trial. Up to 18 patients will be recruited to determine the MTD. Once the MTD has been determined an additional 12 patients will be recruited and treated at the MTD in order to gain further safety and efficacy data. The MTD of Romidepsin in combination with Azacitidine will be determined using an escalating, de-escalating 3+3 cohort design. The first patients will be recruited to Cohort 1 of the study. Patients will receive up to six cycles of the combination therapy (each cycle being 28 days). Each cycle of therapy will consist of Romidepsin infusion on days 8, 15 (and 22 if dose level 3) and seven consecutive days excluding the weekend of subcutaneous injections of Azacitidine, starting on day 1 of a 28 day cycle. The decision as to whether to escalate/de-escalate/expand the cohort will depend on the number of dose-limiting toxicities (DLTs) experienced. There are five cohorts in total which will consist of differing strengths of doses for azacitidine and romidepsin depending on which cohort it is: Cohort (-2): Dose [(Romidepsin (mg/m2): 8 mg/m2 d8, 15; Azacitidine (mg/m2): 55 mg/m2 d1-9 (5,2,2)] Cohort (-1): Dose [(Romidepsin (mg/m2): 8 mg/m2 d8, 15; Azacitidine (mg/m2): 75 mg/m2 d1-9 (5,2,2)] Cohort [1 (starting dose)]: Dose [(Romidepsin (mg/m2): 10 mg/m2 d8, 15; Azacitidine (mg/m2): 75 mg/m2 d1-9 (5,2,2)] Cohort (2): Dose [(Romidepsin (mg/m2): 12 mg/m2 d8, 15; Azacitidine (mg/m2): 75 mg/m2 d1-9 (5,2,2)] Cohort (3): Dose [(Romidepsin (mg/m2): 12 mg/m2 d8, 15, 22; Azacitidine (mg/m2): 75 mg/m2 d1-9 (5,2,2)] |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Romidespin, azacitidine |
| Primary outcome measure | Assessment of MTD of Romidepsin in combination with Azacitidine; Timepoint(s): Once six patients have been treated at the proposed MTD (provided DLT's did not occur in two or more) |
| Secondary outcome measures | 1.Assessment of tolerability and safety of Romidepsin in combination with Azacitidine (graded according to NCI CTCAE version 4) from the date of commencing treatment until 28 days following treatment discontinuation 2. Major response rate (CR, CRi and PR), as defined by Cheson criteria and assessed at the end of cycles 3 and 6 of treatment |
| Overall study start date | 01/10/2013 |
| Completion date | 31/12/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Total final enrolment | 48 |
| Key inclusion criteria | 1. Adults (male & female aged ≥ 16 years) with newly diagnosed, relapsed or refractory AML (except Acute Promyelocytic Leukaemia (APML) as defined by the WHO classification scheme) 2. Patients deemed ineligible for conventional chemotherapy on the grounds of age or comorbidities 3. Patients able to receive treatment as an outpatient 4. Patients must have adequate renal and hepatic function as defined below: Total bilirubin ≤ 2.5 x upper limit of normal (ULN), aspartate aminotransferase / alanine aminotransferase (AST or ALT) ≤ 2.5 x ULN, estimated glomerular filtration rate (eGFR) ≥40mls/min 5. Patients have given written informed consent 6. Be willing to comply with the protocol for the duration of the study 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 |
| Key exclusion criteria | 1. Patients with allergies or contraindications to Romidepsin or Azacitidine 2. Patients with greater than class 3 New York Heart Association (NYHA) cardiac impairment 3. Blastic transformation of chronic myeloid leukaemia (CML) 4. Pregnant or lactating women (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to registration) 5. Females of childbearing potential (i.e. not postmenopausal or surgically sterilised) who are not willing to use adequate methods of contraception to prevent pregnancy or abstain from heterosexual activity for the duration of the trial and for at least 3 months following treatment discontinuation. This includes females who are not willing to use additional methods of contraception in addition to oestrogen containing contraceptives 6. Male patients who are not willing to use an adequate method of contraception for the duration of the trial treatment if engaged in sexual activity with a female of childbearing potential and for at least 3 months following treatment discontinuation 7. Patients with unstable angina, congenital long QT syndrome or a history of myocardial infarction (MI) within the last 6 months 8. Patients with concurrent active malignancy 9. Any co-morbidity that could limit compliance with the trial, including but not limited to the following: 9.1. Uncontrolled hypertension 9.2. Symptomatic congestive heart failure 9.3. Uncontrolled cardiac arrhythmia 9.4. Psychiatric or social conditions that may interfere with patients compliance or any other condition (including laboratory abnormalities) that in the Investigators opinion will affect the patients participation in this trial 10. Patients who have taken any other investigational medicinal product within 4 weeks of study entry 11. Active symptomatic fungal, bacterial, and/or viral infection including known human immunodeficiency virus (HIV) or known viral (A, B or C) Hepatitis 12. Patients who are high medical risks due to non-malignant systemic disease as well as those with active uncontrolled infection |
| Date of first enrolment | 01/10/2013 |
| Date of final enrolment | 06/10/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Website | http://www.birmingham.ac.uk |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Charity
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from the ROMAZA mailbox (romaza@trials.bham.ac.uk). Data anonymised in compliance with the Information Commissioners Office requirements, using a procedure based on guidelines from the Medical Research Council Methodology Hubs, will be available for sharing upon request from the Trial Management Group. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 06/09/2021 | 15/03/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
18/06/2024: Cancer Research UK plain English summary link was updated.
17/03/2022: Total final enrolment number and IPD sharing statement added.
15/03/2022: Publication reference added.
29/01/2019: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 01/10/2014 to 31/12/2019
2. The recruitment end date has been changed from 01/10/2014 to 06/10/2017
3. The intention to publish date has been added
02/02/2017: No publications found, verifying study status with principal investigator.
