Condition category
Cancer
Date applied
11/12/2013
Date assigned
11/12/2013
Last edited
04/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Eszter Nagy

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 7673
romicar@trials.bham.ac.uk

Additional identifiers

EudraCT number

2013-001879-20

ClinicalTrials.gov number

Protocol/serial number

15553

Study information

Scientific title

Phase I/II study to determine the maximum tolerated dose and activity of the combination of Romidepsin and Carfilzomib in relapsed or refractory peripheral T-cell lymphoma

Acronym

RomiCar

Study hypothesis

RomiCar is a prospective, single arm, multicentre phase I/II clinical trial for patients with relapsed or refractory peripheral T-cell lymphoma.

The following designs will be used in each phase:
Phase I: Continual Reassessment Method (CRM) to determine the Maximum Tolerated Dose (MTD) of the combination of romidepsin and carfilzomib.
Phase II: A’Hern’s single stage design to assess the activity (best overall response rate (PR + CR)) of the combination of romidepsin and carfilzomib over 8 cycles of treatment.

Ethics approval

NRES Committee East Midlands - Northampton, 30/12/2013, ref.:13/EM/0462

Study design

Non-randomised interventional treatment trial

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 contact details to request a participant information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Lymphoma; Disease: Lymphoma (non-Hodgkin's)

Intervention

Carfilzomib, Proteasome inhibitor
Romidepsin, Histone deacetylase (HDAC) inhibitor

Romidepsin dose (days 1, 8, 15)
Dose level 1: 8mg/m2
Dose level 2 (starting dose):10mg/m2
Dose level 3: 10mg/m2
Dose level 4: 12mg/m2
Dose level 5: 12mg/m2
Dose level 6: 14mg/m2

Carfilzomib dose* (days 1, 2, 8, 9, 15, 16)
Dose level 1: 20/36mg/m2
Dose level 2 (starting dose):20/36mg/m2
Dose level 3: 20/45mg/m2
Dose level 4: 20/45mg/m2
Dose level 5: 20/56mg/m2
Dose level 6: 20/56mg/m2

* For all dose levels, the carfilzomib dose will be 20mg/m2 for the first 2 doses (i.e. day 1 and 2 of cycle 1), rising to the target dose for subsequent doses and cycles.

Patients in the phase II will receive the Maximum Tolerated Dose determined by the phase I.
Treatment is intravenous and given in cycles (each lasting 28 days). Treatment is given on the days stated in the table above. Patients will receive treatment for 8 cycles and further cycles may be given at the investigators discretion if the patient has not progressed. Follow-up is a minimum of 1 year.

Follow Up Length: 12 month(s)
Study Entry : Registration only

Intervention type

Drug

Phase

Phase I/II

Drug names

Romidepsin, Carfilzomib

Primary outcome measures

Maximum Tolerated Dose (MTD) of the combination of romidepsin and carfilzomib (Phase I); Timepoint(s): Within 4 weeks of treatment with the combination

Secondary outcome measures

1. Best Overall Response Rate (Phase II); Timepoint(s): During 8 cycles of treatment with the combination
2. Duration of response from time of first documented response until relapse or progression; Timepoint(s): From first response through to end of follow-up
3. Maximum % change in the radiological sum of the products of the diameters from baseline; Timepoint(s): During 8 cycles of combination treatment
4. Overall Survival; Timepoint(s): From baseline to 6, 12, 24 and 36 months
5. Progression Free Survival (Phase II); Timepoint(s): From baseline to 6, 12, 24 and 36 months
6. Toxicity of the combination of romidepsin and carfilzomib; Timepoint(s): During combination treatment

Overall trial start date

13/07/2015

Overall trial end date

13/07/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age ≥ 16 years of age
2. Life expectancy > 12 weeks
3. ECOG performance status ≤ 2
4. Relapsed or refractory* peripheral Tcell lymphoma including the following histologies: peripheral Tcelllymphoma not otherwise specified, angioimmunoblastic Tcell lymphoma, anaplastic large cell lymphoma, enteropathy associated Tcell lymphoma, extranodal NK/Tcell lymphoma, transformed mycosis fungoides, hepatosplenic Tcell lymphoma
5. Failed at least 1 prior therapy (but no upper limit of prior regimens)
6. Adequate haematopoietic reserve (Hb ≥ 9g/dl, neutrophils ≥ 1.0x109/l and platelets ≥ 100x109/l or ≥ 75x109/l if marrow involvement documented)
7. Adequate liver function (bilirubin ≤ 1.5 x ULN, AST / ALT ≤ 2x ULN)
8. Adequate renal function (creatinine clearance ≥ 20ml/min as assessed by Cockcroft and Gault calculation)
9. Serum potassium ≥ 4.0 mmol/l, calcium ≥ 2.2 mmol/l and magnesium ≥ 0.85 mmol/l prior to trial entry
10. CT measurable disease with at least 1 lesion having short axis > 1.5cm or splenomegaly > 14cm in craniocaudal
length attributable to relapsed lymphoma
11. Ability to give informed consent
* For all relapsed patients, relapse must be confirmed by tissue biopsy (or bone marrow trephine if no other tissue available). For refractory patients, a biopsy must have been obtained within the last 6 months and preferably to confirm refractory disease.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 57; UK Sample Size: 57

Participant exclusion criteria

1. Persistent treatment related toxicities of CTCAE v4.0 grade ≥ 2
2. Previous treatment with histone deactylase inhibitor or proteasome inhibitor
3. Need for any other concurrent anticancer drug (apart from corticosteroids at a dose equivalent to prednisolone ≤7.5mg daily). A steroid prephase may be used but should be stopped by the first day of cycle 1.
4. Concurrent medical illness deemed by the investigator as uncontrolled and/or clinically significant
5. Coexisting active infection requiring parenteral antibiotics
6. Patients unable to swallow oral medication
7. Active infection with HIV, hepatitis B or hepatitis C
8. Radiotherapy* (except for palliative reasons), endocrine therapy, immunotherapy or use of other investigationalagents within 28 days prior to trial entry (or a longer period depending on the defined characteristics of the agents used, please contact the trials office for confirmation). *Limited field radiotherapy to an isolated lesion in bone or soft tissue must be completed 2 weeks prior to trial entry
9. Major surgery within 4 weeks of trial entry
10. Patients with proven CNS involvement
11. QTc interval of ≥ 480ms or patients taking medications that significantly prolong the QT interval (Appendix 7)
12. Clinically significant cardiac disease ≥ NYHA Class III, symptomatic ischaemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within 6 months of trial entry
13. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry and within 7 days prior to the start of treatment. Postmenopausal females (> 45 years old and without menstruation for > 1 year) and surgically sterilised females are exempt from a pregnancy test)
14. Patients and partners of childbearing potential not willing to use effective contraception during and for 3 months after therapy

Recruitment start date

13/07/2015

Recruitment end date

13/07/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Christie Hospital
Manchester
M20 4BX
United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Derriford Hospital
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Guy's Hospital
London
SE1 9RT
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St Bartholomew's Hospital
London
EC1A 7BE
United Kingdom

Trial participating centre

St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

The Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Trial participating centre

University College London Hospital
London
NW1 2BU
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
-
RomiCar@trials.bham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Celgene Europe Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Leukaemia & Lymphoma Research; Grant Codes: 13018 TAP Trial

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Onyx Therapeutics, Inc.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

13/07/2021

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

04/08/2016: the following changes were made to the trial record: 1. The overall trial start date was changed from 01/02/2014 to 13/07/2015. 2. The overall trial end date was changed from 01/02/2016 to 13/07/2020. 3. The recruitment start date was changed from 01/02/2014 to 13/07/2015. 4. The recruitment end date was changed from 01/02/2016 to 13/07/2018.