Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Mrs Nadira Jilani
ORCID ID
Contact details
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
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romaza@trials.bham.ac.uk
Additional identifiers
EudraCT number
2011-005023-40
ClinicalTrials.gov number
Protocol/serial number
15082
Study information
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
Acronym
ROMAZA
Study hypothesis
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
NRES Committee South Central Oxford C, First MREC approval date 08/05/2013, ref: 13/SC/0157
Study design
Non-randomised interventional and observational; Design type: Treatment, Cohort study
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 use the contact details to request a patient information sheet
Condition
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
Phase
Phase I
Drug names
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 trial start date
01/10/2013
Overall trial end date
01/10/2014
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 30; UK Sample Size: 30
Participant 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
Recruitment start date
01/10/2013
Recruitment end date
01/10/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
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
Basic results (scientific)
Publication list