Myelodysplastic SyndromesPhase 2NCT02228525
Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes
A Phase 2 study testing selinexor (KPT-330) in people with Myelodysplastic Syndromes, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to see if selinexor will improve the blood counts and bone marrow function in people with your type of MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- selinexor (KPT-330)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2014to 6 Apr 2021
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent in accordance with federal, local, and institutional guidelines
- Age ≥18 years
- Patients with Myelodysplastic Syndromes refractory (primary or acquired resistance) to hypomethylating agents(decitabine or 5-azacytidine). At least 4 1- month cycles of prior decitabine or SGI-110 OR 6 1-month cycles of 5-azacytidine (IV, subcutaneous, or oral is required unless the patient has progressive disease prior to completing the required number of cycles.
- Histologically confirmed diagnosis of a Myelodysplastic Syndrome, meeting criteria for any subtype in the FAB or WHO classification systems with any IPSS score.
- Patients with MDS who relapse after allogeneic stem cell transplant are eligible if they received standard dose decitabine or 5-azacytidine prior to or after stem cell transplant as defined in inclusion criteria 3.
- If patient has undergone prior allogeneic stem cell transplant, they must be greater than 100 days post transplant and have ≤ grade 2 graft-versus-host disease
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- There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Patients receiving erythropoietin (darbepoetin, epoetin alfa) must be on a stable dose and with stable transfusion requirement or hemoglobin level during the 8 weeks prior to study entry.
- Adequate hepatic function within 21 days prior to C1D1: total bilirubin <2 times the upper limit of normal (ULN), asparate aminotransferase (AST) <2.5 times ULN and alanine aminotransferase (ALT) <2.5 times ULN.
- Adequate renal function within 21 days prior to C1D1: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault.
- Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and 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.
Who cannot join
- Patients who are pregnant or lactating;
- Chemotherapy or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1. Hydroxyurea may be continued until 72 hours prior to first dose and at least 24 hours before the baseline bone marrow aspiration is performed;
- Major surgery within four weeks before Day 1;
- Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (ie: ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), congestive heart failure (CHF) of NYHA Class ≥3, or myocardial infarction (MI) within 3 months;
- Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within one week prior to first dose; Prophylactic antimicrobials are permitted.
- Known to be HIV seropositive;
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- Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen);
- Patients with another active malignancy. Asymptomatic sites of disease are not considered active. Treated or untreated sites of disease may be considered inactive if they are stable for at least 2 months and are not expected to require therapy for 4 months.
- Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
- Grade ≥2 peripheral neuropathy at baseline (within 21 days prior to cycle 1 day 1).
- History of seizures, movement disorders or cerebrovascular accident within the past 1 years prior to cycle 1 day 1.
- Patients with macular degeneration with markedly decreased visual acuity, patients with markedly decreased visual acuity (no specific etiology) or uncontrolled glaucoma.
- Patients who are significantly below their ideal body weight (BMI < 17)..
- Serious psychiatric or medical conditions that could interfere with treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase II Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes
The purpose of this study is to see if selinexor will improve the blood counts and bone marrow function in people with your type of MDS.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- selinexor (KPT-330)
- Keywords
- Selinexor (KPT-330), Selective Inhibitor of Nuclear Export (SINE), 14-005
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
selinexor (KPT-330)Drug
| Study group | Role | What they receive |
|---|---|---|
| selinexor (KPT-330) | Experimental | Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. Receives: Drug: selinexor (KPT-330) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate
Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.
Measured: 2 years
Secondary outcomes (3)
Response Duration
Response duration will be calculated among patients who achieve a response of HI, mCR, PR or CR using Kaplan-Meier methodology. Median duration of response and the corresponding 95% confidence interval will be estimated.
Measured: 2 years
Overall Survival
Overall survival from the time of study enrollment will be calculated using Kaplan-Meier methodology. Overall survival curves will be displayed for the study population along with selected quantiles and corresponding 95% confidence intervals of survival.
Measured: 2 years
Participants Evaluated for Adverse Events
The safety and tolerability of Selinexor and ST will be evaluated by means of drug related AE reports, physical examinations, and laboratory safety evaluations. Common Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study start27 Aug 2014
- Primary completion6 Apr 2021
- Study completion6 Apr 2021
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 Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- M.D. Anderson Cancer Center, Columbia University, Karyopharm Therapeutics Inc
- Responsible party
- Sponsor
- Investigators
- Virginia Klimek, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228525
- Sponsor's protocol ID
- 14-005
- Status last verified
- Apr 2021
- First submitted
- 27 Aug 2014
- Last updated
- 9 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Taylor J, Mi X, Penson AV, Paffenholz SV, Alvarez K, Sigler A, Chung SS, Rampal RK, Park JH, Stein EM, Tallman MS, Sen F, Gonen M, Abdel-Wahab O, Klimek VM. Safety and activity of selinexor in patients with myelodysplastic syndromes or oligoblastic acute myeloid leukaemia refractory to hypomethylating agents: a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2020 Aug;7(8):e566-e574. doi: 10.1016/S2352-3026(20)30209-X.
PubMed 32735836
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT02228525
- Acronym / sponsor ID
- 14-005
- Conditions
- Myelodysplastic Syndromes
- Keywords
- Selinexor (KPT-330), Selective Inhibitor of Nuclear Export (SINE), 14-005
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- M.D. Anderson Cancer Center, Columbia University, Karyopharm Therapeutics Inc
- Study start
- 27 Aug 2014 (actual)
- Primary completion
- 6 Apr 2021 (actual)
- Study completion
- 6 Apr 2021 (actual)
- First posted
- 29 Aug 2014 (estimated)
- Results
- Posted 9 Mar 2022
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 study is to see if selinexor will improve the blood counts and bone marrow function in people with your type of MDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| selinexor (KPT-330) | Experimental | Drug: selinexor (KPT-330)Patients with myelodysplastic syndromes who are refractory to hypomethylating agents (decitabine or 5-azacytidine) will receive oral selinexor at a starting dose of 60 mg twice weekly for 2 weeks, followed by 1 week of no therapy. Dose reductions are permitted for patients who are benefiting from selinexor but have poor tolerance. After discontinuation from treatment, patients will be followed by the study staff for survival status approximately every three months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent in accordance with federal, local, and institutional guidelines
- Age ≥18 years
- Patients with Myelodysplastic Syndromes refractory (primary or acquired resistance) to hypomethylating agents(decitabine or 5-azacytidine). At least 4 1- month cycles of prior decitabine or SGI-110 OR 6 1-month cycles of 5-azacytidine (IV, subcutaneous, or oral is required unless the patient has progressive disease prior to completing the required number of cycles.
- Histologically confirmed diagnosis of a Myelodysplastic Syndrome, meeting criteria for any subtype in the FAB or WHO classification systems with any IPSS score.
- Patients with MDS who relapse after allogeneic stem cell transplant are eligible if they received standard dose decitabine or 5-azacytidine prior to or after stem cell transplant as defined in inclusion criteria 3.
Key exclusion criteria (14 listed)
- Patients who are pregnant or lactating;
- Chemotherapy or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1. Hydroxyurea may be continued until 72 hours prior to first dose and at least 24 hours before the baseline bone marrow aspiration is performed;
- Major surgery within four weeks before Day 1;
- Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (ie: ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), congestive heart failure (CHF) of NYHA Class ≥3, or myocardial infarction (MI) within 3 months;
- Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within one week prior to first dose; Prophylactic antimicrobials are permitted.
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 |
|---|---|---|
| selinexor (KPT-330) | Drug | selinexor (KPT-330) |
Primary outcome
Best Overall Response Rate
Time frame: 2 years
Using a Simon's two-stage minimax design, this trial will accrue a maximum of 20 patients. Early termination may occur if no responses are observed in the first 13 patients. If at least one response is observed, the trial will continue to the maximum sample size. At the end of the trial, the treatment strategy will be considered promising in this patient population if at least 3 patients achieve a response. The type I and type II errors are set at 0.10.
3 secondary outcomes
Response Duration
Time frame: 2 years
Overall Survival
Time frame: 2 years
Participants Evaluated for Adverse Events
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32735836Taylor J, Mi X, Penson AV, Paffenholz SV, Alvarez K, Sigler A, Chung SS, Rampal RK, Park JH, Stein EM, Tallman MS, Sen F, Gonen M, Abdel-Wahab O, Klimek VM. Safety and activity of selinexor in patients with myelodysplastic syndromes or oligoblastic acute myeloid leukaemia refractory to hypomethylating agents: a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2020 Aug;7(8):e566-e574. doi: 10.1016/S2352-3026(20)30209-X.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Virginia Klimek, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing selinexor (KPT-330) in people with Myelodysplastic Syndromes, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
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 14 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 9 Mar 2022. 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 United States. 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 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?
Yes. Results are posted in the registry (first posted 9 Mar 2022). 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?
Best Overall Response Rate (time frame: 2 years). 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 NCT02228525, 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 9 Mar 2022.