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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-romidepsin-azacitidine-acute-myeloid-leukaemia-romaza

Contact information

Mrs Nadira Jilani
Scientific

Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Email romaza@trials.bham.ac.uk

Study information

Study designNon-randomised interventional and observational; Design type: Treatment, Cohort study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleROMAZA: 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 acronymROMAZA
Study objectivesThis 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) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)
InterventionPatients 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 (DLT’s) 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I
Drug / device / biological / vaccine name(s)Romidespin, azacitidine
Primary outcome measureAssessment 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 measures1.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 date01/10/2013
Completion date31/12/2019

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participantsPlanned Sample Size: 30; UK Sample Size: 30
Total final enrolment48
Key inclusion criteria1. 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 criteria1. 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 patient’s 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 enrolment01/10/2013
Date of final enrolment06/10/2017

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Sponsor information

University of Birmingham (UK)
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 logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Charity

Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Location
United Kingdom

Results and Publications

Intention to publish date31/12/2020
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planNot provided at time of registration
IPD sharing planThe 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.