Peripheral T-cell LymphomaPhase 1NCT03212937
Phase I Trial of Selinexor (KPT-330) and Ifosfamide, Carboplatin, Etoposide (ICE) in Peripheral T-cell Lymphoma
A Phase 1 study testing Selinexor and ICE Chemotherapy in people with Peripheral T-cell Lymphoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
This is a single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Peripheral T-cell Lymphoma
- What is being tested?
- Selinexor and ICE Chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Jul 2016to Nov 2020
- Phase
- Phase 1
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed T or NK/T-cell lymphomas including the following histologies:
- Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)
- Angioimmunoblastic T-cell lymphomas (AITL)
- Anaplastic large cell lymphoma (ALCL)
- Natural-killer/T-cell lymphoma (NKTL)
- Patients must have received at least two cycles of one prior regimen administered with curative intent and one of the following:
Show all 28Show fewer
- failed to have achieve at least a partial response after 2 or more cycles
- failed to achieve a complete response after 6 or more cycles
- progressed after an initial response
- For patients who have CD30+ anaplastic large cell lymphoma, they must have failed or are ineligible or intolerant of brentuximab vedotin
- Patients must be age >18 years.
- Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
- Patients must have ECOG performance status of 0-2
- Patients must have laboratory test results within these ranges:
- Absolute neutrophil count ≥1500/mm³
- Platelet count ≥75,000/mm³
- Creatinine clearance ≥40ml/min
- Total bilirubin ≤1.5x ULN. Higher levels are acceptable if these can be attributed to active haemolysis or ineffective erythropoiesis.
- AST (SGOT) and ALT (SGPT) ≤2x ULN
- Women of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test prior to KPT-330 treatment. Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.
- Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal.
- For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
- As the effects of selinexor on the developing human fetus at the recommended therapeutic dose are unknown, women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with selinexor. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women that are pregnant or breastfeeding are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
- Patients must be able to understand and willing to sign a written informed consent document.
- Patients must be able to adhere to the study visit schedule and other protocol requirements.
- Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Men and women of all ethnic groups are eligible for this study
Who cannot join
- Patients who have had prior malignancies (other than T and NK/T-cell lymphomas) for ≤5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- Patients who have had other anti-cancer therapy, including radiation or experimental drug or therapy, within 28 days of enrollment.
- Patients with known HIV, active hepatitis B, active hepatitis C.
- Patients with known central nervous system involvement by lymphoma.
- Patients with known or suspected hypersensitivity to selinexor.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Investigator Sponsored Trial of Selinexor (KPT-330), a Selective Inhibitor of Nuclear Export / SINE™ Compound and Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
This is a single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to examine the study's biologic objectives.
Read the detailed description
STUDY OBJECTIVES:
Primary:
- To determine the maximum tolerated dose (MTD) of selinexor when given in combination with a standard dose regimen of ifosfamide, carboplatin and etoposide (ICE) in patients with relapsed or refractory PTCL
Secondary:
- To assess the response rates (complete and partial), progression-free survival (PFS) and overall survival (OS) in patients with relapsed or refractory PTCL
- To estimate the feasibility of stem cell collection after selinexor and ICE
Laboratory objectives:
- Paired tumor specimens pre and post selinexor will be examined ex vivo for
- Response to chemotherapy agents such as doxorubicin and etoposide
- Nuclear localization of tumor suppressor proteins (p53, p73, FOXO), drug targets (topoisomerase II) and mRNA targets
STUDY DESIGN:
This is a single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to examine the study's biologic objectives.
Dose escalation:
- If 0/3 dose-limiting toxicity (DLT) is observed, dose escalation will continue to the next higher dose level.
- If 1/3 DLT is observed, then 3 additional patients will be enrolled in the same dose level; if no DLT is observed from the additional 3 patients, then dose escalation will continue to the next higher dose level. If any DLT is observed from the additional 3 patients, then the previous lower dose will be chosen as the MTD.
- If ≥ 2/3 DLTs are observed, then the previous lower dose level will be chosen as the MTD and the dose finding procedure will be terminated.
PATIENTS:
Subjects will be enrolled at the National Cancer Centre Singapore (NCCS).
Key eligibility criteria include the following:
- Pathologically confirmed aggressive T-cell lymphomas including the following histologies: PTCL-NOS, AITL, ALCL (independent of ALK status), NK/T-cell lymphoma
- Treatment with at least two cycles of one prior regimen administered with curative intent
- Adequate end-organ and bone marrow function
- Absence of known or suspected CNS involvement
- Absence of active viral hepatitis or uncontrolled HIV
STUDY DURATION:
Based on prior and existing patient volumes and accrual to clinical trials, we expect to enroll 1-2 patients per month. We expect to complete study accrual within 2 years.
TOTAL SAMPLE SIZE:
The MTD will be identified using a standard 3+3. A maximum of 18 patients will be required for this phase I study. An additional 5 patients will be treated at the recommended phase II dose to assess safety and to examine the study's biologic objectives.
DOSING REGIMEN:
Dose escalation schedule for selinexor:
Dose level -1: 20mg
Dose level 1: 40mg
Dose level 2: 60mg
Dose level 3: 80mg
Selinexor will be administered on days 3, 5 and 7 of each chemotherapy cycle and ICE will be administered from day 1. In the expansion phase of the study, selinexor is administered on days -5 and -3 prior to cycle 1 of chemotherapy.
All subjects will receive
(I) Standard dose ICE on a 21-day cycle.
- IV Etoposide 100mg/m^2 on D1-3
- IV Carboplatin AUC 5 on D2 (inpatient) or D1 (outpatient)
- IV Ifosfamide 5g/m^2 on D2 (inpatient) or D1-3 (outpatient) (II) Dexamethasone
- 20mg QD D3-7
- 20mg QD D-5 and D-3 (for patients in the expansion phase)
Patients will receive 2-6 cycles of selinexor and ICE. If determined eligible by their treating physician, patients who demonstrate response will undergo autologous stem cell transplantation anytime following the second cycle of selinexor and ICE. Transplant ineligible patients will complete up to 6 cycles of selinexor and ICE, and those with responses or stable disease are eligible for maintenance selinexor at the discretion of the treating physician. Maintenance selinexor will be administered weekly at the dose of 60mg. Dexamethasone 4-12mg should also be given on the selinexor dosing days.
ASSESSMENT:
CT Neck to pelvis or FDG-PET/CT skull base to mid-thigh to be performed repeated after every 2 cycles on days 17 +/- 3 days except after cycle 2 where FDG-PET/CT will be performed
- Conditions
- Peripheral T-cell Lymphoma
- Being tested
- Selinexor, ICE Chemotherapy
- 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.
SelinexorDrug
Oral KPT-330 is administered on Day 3, 5, and 7 of each 21-day cycle. Starting dose is 40mg will be adjusted according to toxicity
ICE ChemotherapyDrug
Also called Ifosfamide, Carboplatin, Etoposide
IV Ifosfamide 5g/m^2 on Day 2 (inpatient) or D1 (outpatient) of each 21-day cycle
IV Carboplatin AUC 5 on Day 2 (inpatient) or D1-3 (outpatient) of each 21-day cycle
IV Etoposide 100 mg/m^2 on Days 1-3 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Selinexor and ICE Chemotherapy | Experimental | Not described Receives: Drug: Selinexor; Drug: ICE Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment related dose limiting toxicity as assessed by NCI CTCAE v4.0
Measured: The first 3 weeks of treatment
Secondary outcomes (3)
Overall response rate
Responses will be assessed using the revised International Workshop Criteria
Measured: From the start of treatment to the best overall response of Complete or Partial Response is achieved, up to 2 years
Progression-free survival
Measured: From the start of the treatment to the date of documentation of either disease progression or death, up to 2 years
Overall survival
Measured: From the start of treatment to the date of death from any cause, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start1 Jul 2016
- Primary completionNov 2020
- Study completionNov 2020
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tiffany PL Tang, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03212937
- Sponsor's protocol ID
- Karyopharm001
- Status last verified
- Apr 2021
- First submitted
- 28 Jun 2017
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Investigator Sponsored Trial of Selinexor (KPT-330), a Selective Inhibitor of Nuclear Export / SINE™ Compound and Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
- ClinicalTrials.gov ID
- NCT03212937
- Acronym / sponsor ID
- Karyopharm001
- Conditions
- Peripheral T-cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- Nov 2020 (actual)
- Study completion
- Nov 2020 (actual)
- First posted
- 11 Jul 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 single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to examine the study's biologic objectives.
Detailed description
STUDY OBJECTIVES:
Primary:
- To determine the maximum tolerated dose (MTD) of selinexor when given in combination with a standard dose regimen of ifosfamide, carboplatin and etoposide (ICE) in patients with relapsed or refractory PTCL
Secondary:
- To assess the response rates (complete and partial), progression-free survival (PFS) and overall survival (OS) in patients with relapsed or refractory PTCL
- To estimate the feasibility of stem cell collection after selinexor and ICE
Laboratory objectives:
- Paired tumor specimens pre and post selinexor will be examined ex vivo for
- Response to chemotherapy agents such as doxorubicin and etoposide
- Nuclear localization of tumor suppressor proteins (p53, p73, FOXO), drug targets (topoisomerase II) and mRNA targets
STUDY DESIGN:
This is a single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to examine the study's biologic objectives.
Dose escalation:
- If 0/3 dose-limiting toxicity (DLT) is observed, dose escalation will continue to the next higher dose level.
- If 1/3 DLT is observed, then 3 additional patients will be enrolled in the same dose level; if no DLT is observed from the additional 3 patients, then dose escalation will continue to the next higher dose level. If any DLT is observed from the additional 3 patients, then the previous lower dose will be chosen as the MTD.
- If ≥ 2/3 DLTs are observed, then the previous lower dose level will be chosen as the MTD and the dose finding procedure will be terminated.
PATIENTS:
Subjects will be enrolled at the National Cancer Centre Singapore (NCCS).
Key eligibility criteria include the following:
- Pathologically confirmed aggressive T-cell lymphomas including the following histologies: PTCL-NOS, AITL, ALCL (independent of ALK status), NK/T-cell lymphoma
- Treatment with at least two cycles of one prior regimen administered with curative intent
- Adequate end-organ and bone marrow function
- Absence of known or suspected CNS involvement
- Absence of active viral hepatitis or uncontrolled HIV
STUDY DURATION:
Based on prior and existing patient volumes and accrual to clinical trials, we expect to enroll 1-2 patients per month. We expect to complete study accrual within 2 years.
TOTAL SAMPLE SIZE:
The MTD will be identified using a standard 3+3. A maximum of 18 patients will be required for this phase I study. An additional 5 patients will be treated at the recommended phase II dose to assess safety and to examine the study's biologic objectives.
DOSING REGIMEN:
Dose escalation schedule for selinexor:
Dose level -1: 20mg
Dose level 1: 40mg
Dose level 2: 60mg
Dose level 3: 80mg
Selinexor will be administered on days 3, 5 and 7 of each chemotherapy cycle and ICE will be administered from day 1. In the expansion phase of the study, selinexor is administered on days -5 and -3 prior to cycle 1 of chemotherapy.
All subjects will receive
(I) Standard dose ICE on a 21-day cycle.
- IV Etoposide 100mg/m^2 on D1-3
- IV Carboplatin AUC 5 on D2 (inpatient) or D1 (outpatient)
- IV Ifosfamide 5g/m^2 on D2 (inpatient) or D1-3 (outpatient) (II) Dexamethasone
- 20mg QD D3-7
- 20mg QD D-5 and D-3 (for patients in the expansion phase)
Patients will receive 2-6 cycles of selinexor and ICE. If determined eligible by their treating physician, patients who demonstrate response will undergo autologous stem cell transplantation anytime following the second cycle of selinexor and ICE. Transplant ineligible patients will complete up to 6 cycles of selinexor and ICE, and those with responses or stable disease are eligible for maintenance selinexor at the discretion of the treating physician. Maintenance selinexor will be administered weekly at the dose of 60mg. Dexamethasone 4-12mg should also be given on the selinexor dosing days.
ASSESSMENT:
CT Neck to pelvis or FDG-PET/CT skull base to mid-thigh to be performed repeated after every 2 cycles on days 17 +/- 3 days except after cycle 2 where FDG-PET/CT will be performed
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Selinexor and ICE Chemotherapy | Experimental | Drug: Selinexor, Drug: ICE Chemotherapy |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients must have histologically confirmed T or NK/T-cell lymphomas including the following histologies:
- Patients must have received at least two cycles of one prior regimen administered with curative intent and one of the following:
- Patients must be age >18 years.
- Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
- Patients must have ECOG performance status of 0-2
Key exclusion criteria (5 listed)
- Patients who have had prior malignancies (other than T and NK/T-cell lymphomas) for ≤5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- Patients who have had other anti-cancer therapy, including radiation or experimental drug or therapy, within 28 days of enrollment.
- Patients with known HIV, active hepatitis B, active hepatitis C.
- Patients with known central nervous system involvement by lymphoma.
- Patients with known or suspected hypersensitivity to selinexor.
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 |
|---|---|---|
| SelinexorOral KPT-330 is administered on Day 3, 5, and 7 of each 21-day cycle. Starting dose is 40mg will be adjusted according to toxicity | Drug | Selinexor and ICE Chemotherapy |
| ICE ChemotherapyAlso: Ifosfamide, Carboplatin, EtoposideIV Ifosfamide 5g/m^2 on Day 2 (inpatient) or D1 (outpatient) of each 21-day cycle IV Carboplatin AUC 5 on Day 2 (inpatient) or D1-3 (outpatient) of each 21-day cycle IV Etoposide 100 mg/m^2 on Days 1-3 of each 21-day cycle | Drug | Selinexor and ICE Chemotherapy |
Primary outcome
Number of participants with treatment related dose limiting toxicity as assessed by NCI CTCAE v4.0
Time frame: The first 3 weeks of treatment
3 secondary outcomes
Overall response rate
Time frame: From the start of treatment to the best overall response of Complete or Partial Response is achieved, up to 2 years
Progression-free survival
Time frame: From the start of the treatment to the date of documentation of either disease progression or death, up to 2 years
Overall survival
Time frame: From the start of treatment to the date of death from any cause, up to 2 years
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 28 Apr 2021.
- Individual participant dataSharing planned: No
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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.
Tiffany PL Tang principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor and ICE Chemotherapy in people with Peripheral T-cell Lymphoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 28 inclusion and 5 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 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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?
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?
Number of participants with treatment related dose limiting toxicity as assessed by NCI CTCAE v4.0 (time frame: The first 3 weeks of treatment). 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 28 Apr 2021.