Peripheral T Cell LymphomaPhase 1/2RomiCarNCT03141203
Evaluation of the Combination of Romidepsin and Carfilzomib in Relapsed/Refractory Peripheral T Cell Lymphoma Patients
A Phase 1/2 study testing Romidepsin and Carfilzomib in people with Peripheral T Cell Lymphoma, run by University of Birmingham at 13 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Peripheral T Cell Lymphoma
- What is being tested?
- Romidepsin and Carfilzomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- 13 Jul 2015to 23 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- Adequate haematopoietic reserve (Hb ≥ 9g/dl, neutrophils ≥ 1.0x10^9/l and platelets ≥ 100x10^9/l or ≥ 75x10^9/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
Who cannot join
- 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
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- 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%
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United Kingdom13 sites
Queen Elizabeth Hospital
Birmingham
St James's University Hospital
Leeds
Leicester Royal Infirmary
Leicester
Clatterbridge Cancer Centre
Liverpool
Guy's Hospital
London
St Bartholomew's Hospital
London
University College London Hospitals
London
Christie Hospital
Manchester
Nottingham University Hospitals
Nottingham
Churchill Hospital
Oxford
Derriford Hospital
Plymouth
Southampton General Hospital
Southampton
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
About this study
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
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.
Read the detailed description
This is a prospective, single arm, phase I/II, multicentre, dose finding study of romidepsin in combination with carfilzomib.
The aim of the phase I is to establish the MTD of the combination using a restricted two-stage CRM. The MTD is defined as the dose level that is closest to the level at which 25% of patients experience a DLT over the first cycle of treatment.
The intention in phase I is to evaluate the DLT-inducing effects of doses in cohorts of patients. Patients will be treated in cohorts at a dose level and each patient will be evaluated for presence or absence of DLT. In stage I, the first cohort of 3 patients will be enrolled at the starting dose, i.e. dose level 2. If none experiences a DLT, the next cohort of 3 patients will be recruited at the next higher level, i.e. dose level 3. This escalation routine will continue until the first DLT is observed or the maximum recruitment for stage I is reached. As soon as the first DLT is observed, dose escalation and de-escalation will be guided by the CRM design that will recommend the dose believed to have associated DLT-rate closest to 25%. If the trial escalates, each dose below the newly tested dose is regarded as being tolerable.
In stage II, we will consider variable cohort sizes of up to eight patients. Patients are screened for eligibility before they are formally registered. During screening, we expect it to transpire that some patients will be ineligible. To maximise recruitment and reduce trial suspension period between cohorts in this rare disease, we will allow for the flexibility of variable cohort sizes by screening cohorts of up to eight patients. We will allocate screening slots so that the sum of: a) the number of patients already receiving treatment in the current cohort; and (b) the number of patients in screening; does not exceed eight. If a patient is screened and proves to be eligible, they will be recruited to the trial. The first three patients in a cohort will receive the dose-level allocated to the cohort. Patients who are inevaluable, as described immediately above, can be replaced. If the fourth to eighth patients are recruited to a cohort and the dose allocated to the cohort is not yet regarded as tolerable, the fourth to eighth patients will receive the next dose-level below. Otherwise, they will receive the same dose level as the previous patients in the cohort. The aim of the described strategy is to maximise recruitment but not expose more than three patients to a dose that has not yet been demonstrated tolerable. The model will be updated regularly and subsequent recommended doses will be assigned to patients iteratively until the maximum sample size is reached, or the trial is stopped early because there is a high chance that the lowest dose is too toxic. It is expected that the CRM will likely allocate patients to the eventual MTD at the later stage of the trial as more data accumulate. Recruitment will be permitted to continue seamlessly to the Phase II component at the latest recommended MTD dose, in consultation with the Trial Safety Committee, unless it is considered necessary to halt recruitment The initial guess of MTD is at dose combination level 4, however to exercise caution, dose level 2 is defined as the starting dose level.
Dose Levels
- 8mg/m2 Romidepsin (days 1, 8, 15), 20/36mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- (Starting dose) 10mg/m2 Romidepsin (days 1, 8, 15), 20/36mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 10mg/m2 Romidepsin (days 1, 8, 15), 20/45mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 12mg/m2 Romidepsin (days 1, 8, 15), 20/45mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 12mg/m2 Romidepsin (days 1, 8, 15), 20/56mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 14mg/m2 Romidepsin (days 1, 8, 15), 20/56mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16) 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.
Once the MTD is defined, patients recruited at a lower dose may receive the MTD for any subsequent cycles of treatment at the discretion of the treating Investigator and the Chief Investigator.
The phase II component will aim to provide a preliminary estimate of activity in 28 patients at the MTD combination established in phase I. The phase II component is based on A'Hern's single arm, single stage design and would utilise patients allocated to the MTD in phase I. Patients will be recruited over a 36-month period and will receive a minimum of 8 cycles of treatment. Patients will continue to be followed up for progression and survival until the end of the trial.
- Conditions
- Peripheral T Cell Lymphoma
- Being tested
- Romidepsin, Carfilzomib
- Medical subject headings
- Lymphoma, T-Cell, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomidepsinDrug
Also called Istodax
10mg vial for Injection
CarfilzomibDrug
Also called Kyprolis
60mg vial for injection
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
| Dose Level 2 (starting dose) | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
| Dose Level 3 | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
| Dose Level 4 | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
| Dose Level 5 | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
| Dose Level 6 | Experimental | 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. Receives: Drug: Romidepsin; Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of the combination of romidepsin and carfilzomib
MTD as determined by the continual reassessment model (CRM) with a predefined target Dose Limiting Toxicity (DLT) probability of 25%
Measured: Cycle 1 (each cycle is 28 days)
Best overall response rate (PR + CR) at the MTD
Assessed using the International response criteria
Measured: Data will be collected over the first 8 cycles of therapy (each cycle is 28 days)
Secondary outcomes (6)
Toxicity of the combination of romidepsin and carfilzomib
Assessed using CTCAE v4
Measured: Adverse events information will be collected throughout the 36 month recruitment period of the trial and during the one year follow up period
Best overall response at the MTD
Assessed using International response criteria
Measured: Information relating to this outcome will be collected up to and including the one year follow-up time point
Maximum percentage change in the radiological sum of the product of the diameters from baseline, assessed using the Revised Response Criteria for Malignant Lymphoma
Assessed on suitable target and non-target lesions
Measured: Information relating to this outcome will be collected up to and including the one year follow-up time point
Duration of response from time of first documented response until relapse or progression
Measured: Information relating to this outcome will be collected up to and including the one year follow-up time point
Progression free survival
Measured: Information relating to this outcome will be collected up to and including the one year follow-up time point
Overall survival
Measured: Information relating to this outcome will be collected up to and including the one year follow-up time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2017
- Study start13 Jul 2015
- Primary completionAug 2020
- Study completion23 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral T Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Graham Collins, MBBS DPhil, Principal investigator, Churchill Hospital, Oxford, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03141203
- Sponsor's protocol ID
- RG_13-107
- Other IDs
- 2013-001879-20
- Acronym
- RomiCar
- Status last verified
- May 2022
- First submitted
- 21 Feb 2017
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03141203
- Acronym / sponsor ID
- RomiCar / RG_13-107
- Conditions
- Peripheral T Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Bloodwise, Celgene, Amgen
- Study start
- 13 Jul 2015 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- 23 Sep 2021 (actual)
- First posted
- 5 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, single arm, phase I/II, multicentre, dose finding study of romidepsin in combination with carfilzomib.
The aim of the phase I is to establish the MTD of the combination using a restricted two-stage CRM. The MTD is defined as the dose level that is closest to the level at which 25% of patients experience a DLT over the first cycle of treatment.
The intention in phase I is to evaluate the DLT-inducing effects of doses in cohorts of patients. Patients will be treated in cohorts at a dose level and each patient will be evaluated for presence or absence of DLT. In stage I, the first cohort of 3 patients will be enrolled at the starting dose, i.e. dose level 2. If none experiences a DLT, the next cohort of 3 patients will be recruited at the next higher level, i.e. dose level 3. This escalation routine will continue until the first DLT is observed or the maximum recruitment for stage I is reached. As soon as the first DLT is observed, dose escalation and de-escalation will be guided by the CRM design that will recommend the dose believed to have associated DLT-rate closest to 25%. If the trial escalates, each dose below the newly tested dose is regarded as being tolerable.
In stage II, we will consider variable cohort sizes of up to eight patients. Patients are screened for eligibility before they are formally registered. During screening, we expect it to transpire that some patients will be ineligible. To maximise recruitment and reduce trial suspension period between cohorts in this rare disease, we will allow for the flexibility of variable cohort sizes by screening cohorts of up to eight patients. We will allocate screening slots so that the sum of: a) the number of patients already receiving treatment in the current cohort; and (b) the number of patients in screening; does not exceed eight. If a patient is screened and proves to be eligible, they will be recruited to the trial. The first three patients in a cohort will receive the dose-level allocated to the cohort. Patients who are inevaluable, as described immediately above, can be replaced. If the fourth to eighth patients are recruited to a cohort and the dose allocated to the cohort is not yet regarded as tolerable, the fourth to eighth patients will receive the next dose-level below. Otherwise, they will receive the same dose level as the previous patients in the cohort. The aim of the described strategy is to maximise recruitment but not expose more than three patients to a dose that has not yet been demonstrated tolerable. The model will be updated regularly and subsequent recommended doses will be assigned to patients iteratively until the maximum sample size is reached, or the trial is stopped early because there is a high chance that the lowest dose is too toxic. It is expected that the CRM will likely allocate patients to the eventual MTD at the later stage of the trial as more data accumulate. Recruitment will be permitted to continue seamlessly to the Phase II component at the latest recommended MTD dose, in consultation with the Trial Safety Committee, unless it is considered necessary to halt recruitment The initial guess of MTD is at dose combination level 4, however to exercise caution, dose level 2 is defined as the starting dose level.
Dose Levels
- 8mg/m2 Romidepsin (days 1, 8, 15), 20/36mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- (Starting dose) 10mg/m2 Romidepsin (days 1, 8, 15), 20/36mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 10mg/m2 Romidepsin (days 1, 8, 15), 20/45mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 12mg/m2 Romidepsin (days 1, 8, 15), 20/45mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 12mg/m2 Romidepsin (days 1, 8, 15), 20/56mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16)
- 14mg/m2 Romidepsin (days 1, 8, 15), 20/56mg/m2 Carfilzomib (days 1, 2, 8, 9, 15, 16) 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.
Once the MTD is defined, patients recruited at a lower dose may receive the MTD for any subsequent cycles of treatment at the discretion of the treating Investigator and the Chief Investigator.
The phase II component will aim to provide a preliminary estimate of activity in 28 patients at the MTD combination established in phase I. The phase II component is based on A'Hern's single arm, single stage design and would utilise patients allocated to the MTD in phase I. Patients will be recruited over a 36-month period and will receive a minimum of 8 cycles of treatment. Patients will continue to be followed up for progression and survival until the end of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Romidepsin, Drug: Carfilzomib8mg/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. |
| Dose Level 2 (starting dose) | Experimental | Drug: Romidepsin, Drug: Carfilzomib10mg/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. |
| Dose Level 3 | Experimental | Drug: Romidepsin, Drug: Carfilzomib10mg/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. |
| Dose Level 4 | Experimental | Drug: Romidepsin, Drug: Carfilzomib12mg/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. |
| Dose Level 5 | Experimental | Drug: Romidepsin, Drug: Carfilzomib12mg/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. |
| Dose Level 6 | Experimental | Drug: Romidepsin, Drug: Carfilzomib14mg/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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomidepsinAlso: Istodax10mg vial for Injection | Drug | Dose Level 1, Dose Level 2 (starting dose), Dose Level 3, Dose Level 4, Dose Level 5, Dose Level 6 |
| CarfilzomibAlso: Kyprolis60mg vial for injection | Drug | Dose Level 1, Dose Level 2 (starting dose), Dose Level 3, Dose Level 4, Dose Level 5, Dose Level 6 |
Primary outcome
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%
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
6 secondary outcomes
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
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
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
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
Progression free survival
Time frame: Information relating to this outcome will be collected up to and including the one year follow-up time point
Overall survival
Time frame: Information relating to this outcome will be collected up to and including the one year follow-up time point
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Individual participant dataSharing planned: No
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Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graham Collins, MBBS DPhil principal investigator
Churchill Hospital, Oxford, UK
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Romidepsin and Carfilzomib in people with Peripheral T Cell Lymphoma, run by University of Birmingham at 13 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of the combination of romidepsin and carfilzomib (time frame: Cycle 1 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.