Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes

NCT02228525 | Completed Phase 2 Results

• 1 other identifier: 14-005
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes

Keywords

Selinexor (KPT-330); Selective Inhibitor of Nuclear Export (SINE); 14-005

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (3)

• Response Duration

  2 years

• Overall Survival

  2 years

• Participants Evaluated for Adverse Events

  2 years

Study Arms (1)

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.

Drug: selinexor (KPT-330)

Interventions

selinexor (KPT-330) DRUG

selinexor (KPT-330)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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;
• 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).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• M.D. Anderson Cancer Center: collaborator
• Columbia University: collaborator
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 32735836 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

selinexor

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Eytan Stein, MD
• Organization: Memorial Sloan Kettering Cancer Center

steine@mskcc.org

646-608-3749

Study Officials

• Virginia Klimek, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: August 29, 2014
• Study Start: August 27, 2014
• Primary Completion: April 6, 2021
• Study Completion: April 6, 2021
• Last Updated: March 9, 2022
• Results First Posted: March 9, 2022

Record last verified: 2021-04

Locations

US (1)