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Trial record 38 of 57 for:    Romidepsin | Phase 2

Evaluation of the Combination of Romidepsin and Carfilzomib in Relapsed/Refractory Peripheral T Cell Lymphoma Patients (RomiCar)

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ClinicalTrials.gov Identifier: NCT03141203
Recruitment Status : Recruiting
First Posted : May 5, 2017
Last Update Posted : June 12, 2018
Sponsor:
Collaborators:
Bloodwise
Celgene
Amgen
Information provided by (Responsible Party):
University of Birmingham

Brief Summary:

This is a multicentre phase I/II trial looking at the combination of romidepsin and carfilzomib.

The aim of the phase I part is to determine the maximum tolerated dose (MTD) of the combination. This part will recruit up to 27 patients, plus possibly an additional 3 patients at the MTD.

The aim of the phase II part is to assess the activity of the combination at the maximum tolerated dose in 28 patients (including at least 6 patients treated at the MTD from phase I).

Patients will receive 8 cycles of romidepsin with carfilzomib and response will be assessed every second cycle. Patients will be followed up for progression and survival until the end of the trial.


Condition or disease Intervention/treatment Phase
Peripheral T Cell Lymphoma Drug: Romidepsin Drug: Carfilzomib Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : July 13, 2015
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Dose Level 1

8mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/36mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis

Experimental: Dose Level 2 (starting dose)

10mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/36mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis

Experimental: Dose Level 3

10mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/45mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis

Experimental: Dose Level 4

12mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/45mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis

Experimental: Dose Level 5

12mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/56mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis

Experimental: Dose Level 6

14mg/m2 Romidepsin (administered on days 1, 8, 15) and 20/56mg/m2 Carfilzomib (administered days 1, 2, 8, 9, 15, 16) over 8 cycles of treatment.

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.

Drug: Romidepsin
10mg vial for Injection
Other Name: Istodax

Drug: Carfilzomib
60mg vial for injection
Other Name: Kyprolis




Primary Outcome Measures :
  1. Maximum Tolerated Dose of the combination of romidepsin and carfilzomib [ Time Frame: Cycle 1 (each cycle is 28 days) ]
    MTD as determined by the continual reassessment model (CRM) with a predefined target Dose Limiting Toxicity (DLT) probability of 25%

  2. Best overall response rate (PR + CR) at the MTD [ Time Frame: Data will be collected over the first 8 cycles of therapy (each cycle is 28 days) ]
    Assessed using the International response criteria


Secondary Outcome Measures :
  1. Toxicity of the combination of romidepsin and carfilzomib [ Time Frame: Adverse events information will be collected throughout the 36 month recruitment period of the trial and during the one year follow up period ]
    Assessed using CTCAE v4

  2. Best overall response at the MTD [ Time Frame: Information relating to this outcome will be collected up to and including the one year follow-up time point ]
    Assessed using International response criteria

  3. Maximum percentage change in the radiological sum of the product of the diameters from baseline, assessed using the Revised Response Criteria for Malignant Lymphoma [ Time Frame: Information relating to this outcome will be collected up to and including the one year follow-up time point ]
    Assessed on suitable target and non-target lesions

  4. Duration of response from time of first documented response until relapse or progression [ Time Frame: Information relating to this outcome will be collected up to and including the one year follow-up time point ]
  5. Progression free survival [ Time Frame: Information relating to this outcome will be collected up to and including the one year follow-up time point ]
  6. Overall survival [ Time Frame: Information relating to this outcome will be collected up to and including the one year follow-up time point ]


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 16 years of age
  • Life expectancy > 12 weeks
  • ECOG performance status ≤ 2
  • Relapsed or refractory peripheral T-cell lymphoma including the following histologies: peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, enteropathy associated T-cell lymphoma, extranodal NK/T-cell lymphoma, transformed mycosis fungoides, hepatosplenic T-cell lymphoma [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. In rare cases (such as when re-biopsy is not possible), the initial diagnostic biopsy may be accepted, provided that the patient has been reviewed at the local MDT who agreed that the presentation is consistent with relapsed/refractory T cell lymphoma, and this has been documented.]
  • Failed at least 1 prior therapy (but no upper limit of prior regimens)
  • Patients MAY have had a prior allogeneic stem cell transplant but must not require systemic immunosuppression for graft-versus-host disease (local treatments are permitted)
  • Adequate haematopoietic reserve (Hb ≥ 9g/dl, neutrophils ≥ 1.0x109/l and platelets ≥ 100x109/l or ≥ 75x109/l if marrow involvement documented)
  • Adequate liver function (bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to Gilbert's syndrome), AST / ALT ≤ 2x ULN)
  • Adequate renal function (creatinine clearance ≥ 20ml/min as assessed by Cockcroft and Gault calculation)
  • Serum potassium ≥ 3.8 mmol/l, calcium ≥ 2.2 mmol/l and magnesium ≥ LLN prior to trial entry (supplements permitted)
  • CT measurable disease with at least 1 lesion having short axis > 1.5cm or splenomegaly > 14cm in cranio-caudal length attributable to relapsed lymphoma
  • Ability to give informed consent

Exclusion Criteria:

  • Persistent treatment related toxicities of CTCAE v4.0 grade ≥ 2
  • Previous treatment with histone deactylase inhibitor or proteasome inhibitor
  • Need for any other concurrent anti-cancer 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.
  • Concurrent medical illness deemed by the investigator as uncontrolled and/or clinically significant
  • Previous systemic malignancy within the last 3 years unless treated with curative intent with no sign of recurrence. Other exceptions include non-melanotic skin cancer or carcinoma in-situ of the uterine cervix
  • Co-existing active infection requiring parenteral antibiotics
  • Patients unable to swallow oral medication
  • Active infection with HIV, hepatitis B or hepatitis C
  • Radiotherapy* (except for palliative reasons), endocrine therapy, immunotherapy or use of other investigational agents 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
  • Major surgery within 4 weeks of trial entry
  • Patients with proven CNS involvement
  • QTc interval of >450ms or patients taking medications that significantly prolong the QT interval
  • Patients taking any inhibitors or strong inducers of CYP3A4, with the exception of dexamethasone.
  • Clinically significant cardiac disease ≥ NYHA Class III, symptomatic ischaemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within 6 months of trial entry
  • 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)
  • Patients and partners of childbearing potential not willing to use effective contraception during and for 3 months after therapy
  • Concurrent Pulmonary Hypertension
  • Left Ventricular Ejection Fraction (LVEF) of <40%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03141203


Contacts
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Contact: Eszter Nagy +44 (0)121 371 7862 RomiCar@trials.bham.ac.uk

Locations
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United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Principal Investigator: Ram Malladi         
St James's University Hospital Recruiting
Leeds, United Kingdom
Principal Investigator: Rod Johnson         
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom
Principal Investigator: Simon Wagner         
Clatterbridge Cancer Centre Recruiting
Liverpool, United Kingdom
Principal Investigator: Nagesh Kalakonda         
Guy's Hospital Recruiting
London, United Kingdom
Principal Investigator: Paul Fields         
St Bartholomew's Hospital Recruiting
London, United Kingdom
Principal Investigator: Jeff Davies         
University College London Hospitals Recruiting
London, United Kingdom
Principal Investigator: Kate Cwynarski         
Christie Hospital Recruiting
Manchester, United Kingdom
Principal Investigator: Kim Linton         
Nottingham University Hospitals Recruiting
Nottingham, United Kingdom
Principal Investigator: Chris Fox         
Churchill Hospital Recruiting
Oxford, United Kingdom
Principal Investigator: Graham Collins         
Derriford Hospital Recruiting
Plymouth, United Kingdom
Principal Investigator: David Lewis         
Southampton General Hospital Recruiting
Southampton, United Kingdom
Principal Investigator: Andrew Davies         
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Principal Investigator: Dima El-Sharkawi         
Sponsors and Collaborators
University of Birmingham
Bloodwise
Celgene
Amgen
Investigators
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Principal Investigator: Graham Collins, MBBS DPhil Churchill Hospital, Oxford, UK

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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT03141203     History of Changes
Other Study ID Numbers: RG_13-107
2013-001879-20 ( EudraCT Number )
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Romidepsin
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibiotics, Antineoplastic
Antineoplastic Agents