Myelodysplastic Syndromes
Conditions
Keywords
Selinexor (KPT-330), Selective Inhibitor of Nuclear Export (SINE), 14-005
Brief 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.
Interventions
Sponsors
M.D. Anderson Cancer Center
Columbia University
Karyopharm Therapeutics Inc
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Duration | 2 years | 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. |
| Overall Survival | 2 years | 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. |
| Participants Evaluated for Adverse Events | 2 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
selinexor (KPT-330) | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Selinexor (KPT-330) |
|---|---|
| Age, Continuous | 77 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 25 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor (KPT-330) | Best Overall Response Rate | 26 Percentage of participants with response |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor (KPT-330) | Overall Survival | 8.5 months |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selinexor (KPT-330) | Participants Evaluated for Adverse Events | 25 Participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor (KPT-330) | Response Duration | 6.3 months |