Condition category
Cancer
Date applied
27/09/2013
Date assigned
27/09/2013
Last edited
14/03/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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
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.

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=15082

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 controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below 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 (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 type

Drug

Phase

Phase I

Drug names

romidespin, azacitidine

Primary outcome measures

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

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 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.

Recruitment start date

01/10/2013

Recruitment end date

01/10/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Clinical Haematology
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

http://www.birmingham.ac.uk

Funders

Funder type

Charity

Funder name

Leukaemia & Lymphoma Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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