Peripheral T-Cell LymphomaPhase 1NCT01401530
E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma
A Phase 1 study testing denileukin diftitox (E7777) in people with Peripheral T-Cell Lymphoma, run by Eisai Co., Ltd. at 4 sites in Japan.
Trial summary
The purpose of this Phase 1 study is to determine the maximum tolerated dose (MTD) through observation of dose limiting toxicity (DLT), which is in advance defined, in patients with peripheral or cutaneous T-cell lymphoma. Read more about this study
- Who is it for?
- Ages 20 to 79 years
- Conditions the study is for
- Peripheral T-Cell Lymphoma
- What is being tested?
- denileukin diftitox (E7777)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesJapan
- Study dates
- Jul 2011to Jan 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Brain metastasis with clinical symptoms which requires treatment
- Serious systemic infection requiring intensive treatment
- Serious complications or histories
- History of hypersensitivity to protein therapeutics
- Known to be positive for HIV antibody, HCV antibody, or HBs antigen
- History of malignancy other than peripheral T-cell lymphoma and less than five years have elapsed since the last remission
- Patients who have undergone allogeneic hematopoietic stem cell transplantation
- Patients with a relapse within 6 months after autologous hematopoietic stem-cell transplantation
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Study site
Chuo-ku, Tokyo
Study site
Isehara, Kanagawa
Study site
Kashiwa, Chiba
Study site
Nagoya, Aichi-ken
About this study
Official title: Phase1/1b Clinical Trial of E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma
The purpose of this Phase 1 study is to determine the maximum tolerated dose (MTD) through observation of dose limiting toxicity (DLT), which is in advance defined, in patients with peripheral or cutaneous T-cell lymphoma.
- Conditions
- Peripheral T-Cell Lymphoma
- Being tested
- denileukin diftitox (E7777)
- Keywords
- Neoplasms, Neoplasms by Histologic Type, Lymphoma, Non-Hodgkin, T- Cell, Lymphatic Diseases, Lymphoproliferative Disorders, lmmune System Diseases, lmmunoproliferative Disorders
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Neoplasms, Neoplasms by Histologic Type, Lymphoma, Lymphatic Diseases, Lymphoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
denileukin diftitox (E7777)Biological
E7777 will be administered by intravenous (IV) infusion for 5 days from Day 1 through 5 of each cycle (21 days/cycle) with 8 cycles in maximum for E7777 alone therapy. E7777 dose will be escalated from 6 micro-g/kg/day to 12, 15 and then to 18 in a stepwise fashion.
| Study group | Role | What they receive |
|---|---|---|
| E7777 | Experimental | Not described Receives: Biological: denileukin diftitox (E7777) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants. If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total. The RD was to be comprehensively determined based on the MTD and safety data. Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment.
Measured: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
Secondary outcomes (11)
Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox
Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood coagulation, blood chemistry, and urinalysis values; periodic measurement of vital signs, body weight, 12-lead electrocardiograms (ECGs), Eastern Cooperative Oncology Group performance status, physical examination findings, and ophthalmological examination findings. TEAEs were defined as an AE that had an onset date, or worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to the last assessment. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug. SAEs were defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect.
Measured: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months
Maximum Serum Concentration (Cmax) of Denileukin Diftitox
Cmax was defined as the maximum observed concentration of denileukin diftitox following administration of study treatment on Cycle 1 Day 1 and was obtained directly from the measured serum concentration-time curves. Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a lower limit of quantitation (LLOQ) of 30 nanograms per milliliter (ng/mL). Serum pharmacokinetic (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the median and full range for all participants and expressed as ng/mL.
Measured: Cycle 1 (Day 1)
Time to Cmax (Tmax) of Denileukin Diftitox in Serum
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed in minutes.
Measured: Cycle 1 (Day 1)
Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the median and full range for all participants and expressed as nanograms*minutes per milliliter (ng*min/mL).
Measured: Cycle 1 (Day 1)
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf))
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the median and full range for all participants and expressed as ng*min/mL.
Measured: Cycle 1 (Day 1)
Terminal Phase Rate Constant (λz)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of λz, which was then summarized as the median and full range for all participants and expressed in 1/minutes.
Measured: Cycle 1 (Day 1)
Terminal Elimination Phase Half-life (t1/2)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the median and full range for all participants and expressed in minutes.
Measured: Cycle 1 (Day 1)
Volume of Distribution at Terminal Phase (Vz)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vz, which was then summarized as the median and full range for all participants and expressed as milliliters per kilogram (mL/kg).
Measured: Cycle 1 (Day 1)
Volume of Distribution at Steady State (Vss)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vss, which was then summarized as the median and full range for all participants and expressed as mL/kg.
Measured: Cycle 1 (Day 1)
Total Clearance (CL)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. SerumPK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the median and full range for all participants and expressed as milliliters/minutes/kilograms (mL/min/kg).
Measured: Cycle 1 (Day 1)
Recommended Dose
This endpoint was combined with primary outcome measure, MTD
Measured: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionAug 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tadashi Nakanishi, Study director, Eisai Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01401530
- Sponsor's protocol ID
- E7777-J081-101
- Status last verified
- Apr 2018
- First submitted
- 18 Jul 2011
- Last updated
- 23 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Ohmachi K, Ando K, Ogura M, Uchida T, Tobinai K, Maruyama D, Namiki M, Nakanishi T. E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase I study. Cancer Sci. 2018 Mar;109(3):794-802. doi: 10.1111/cas.13513. Epub 2018 Feb 26.
PubMed 29363235
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase1/1b Clinical Trial of E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01401530
- Acronym / sponsor ID
- E7777-J081-101
- Conditions
- Peripheral T-Cell Lymphoma
- Keywords
- Neoplasms, Neoplasms by Histologic Type, Lymphoma, Non-Hodgkin, T- Cell, Lymphatic Diseases, Lymphoproliferative Disorders, lmmune System Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Eisai Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Aug 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 25 Jul 2011 (estimated)
- Results
- Posted 23 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase 1 study is to determine the maximum tolerated dose (MTD) through observation of dose limiting toxicity (DLT), which is in advance defined, in patients with peripheral or cutaneous T-cell lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| E7777 | Experimental | Biological: denileukin diftitox (E7777) |
Who may qualify
- Ages
- 20 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- Brain metastasis with clinical symptoms which requires treatment
- Serious systemic infection requiring intensive treatment
- Serious complications or histories
- History of hypersensitivity to protein therapeutics
- Known to be positive for HIV antibody, HCV antibody, or HBs antigen
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 |
|---|---|---|
| denileukin diftitox (E7777)E7777 will be administered by intravenous (IV) infusion for 5 days from Day 1 through 5 of each cycle (21 days/cycle) with 8 cycles in maximum for E7777 alone therapy. E7777 dose will be escalated from 6 micro-g/kg/day to 12, 15 and then to 18 in a stepwise fashion. | Biological | E7777 |
Primary outcome
Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
Time frame: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants. If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total. The RD was to be comprehensively determined based on the MTD and safety data. Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment.
11 secondary outcomes
Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox
Time frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months
Maximum Serum Concentration (Cmax) of Denileukin Diftitox
Time frame: Cycle 1 (Day 1)
Time to Cmax (Tmax) of Denileukin Diftitox in Serum
Time frame: Cycle 1 (Day 1)
Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Time frame: Cycle 1 (Day 1)
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf))
Time frame: Cycle 1 (Day 1)
Terminal Phase Rate Constant (λz)
Time frame: Cycle 1 (Day 1)
Terminal Elimination Phase Half-life (t1/2)
Time frame: Cycle 1 (Day 1)
Volume of Distribution at Terminal Phase (Vz)
Time frame: Cycle 1 (Day 1)
Volume of Distribution at Steady State (Vss)
Time frame: Cycle 1 (Day 1)
Total Clearance (CL)
Time frame: Cycle 1 (Day 1)
Recommended Dose
Time frame: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29363235Ohmachi K, Ando K, Ogura M, Uchida T, Tobinai K, Maruyama D, Namiki M, Nakanishi T. E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase I study. Cancer Sci. 2018 Mar;109(3):794-802. doi: 10.1111/cas.13513. Epub 2018 Feb 26.
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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.
Tadashi Nakanishi study director
Eisai Co., Ltd.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing denileukin diftitox (E7777) in people with Peripheral T-Cell Lymphoma, run by Eisai Co., Ltd. at 4 sites in Japan.
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 0 inclusion and 8 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 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (MTD) and Recommended Dose (RD) (time frame: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01401530, which also lists 1 linked publication.
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 23 Nov 2018.