A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML

NCT02403310 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-18157
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established.

Conditions

Leukemia; Acute Myeloid Leukemia; AML

Keywords

adverse-risk AML; poor-risk karyotype; cytogenetic abnormality; poor-risk mutations; antecedent hematologic disorder; treatment related AML

Outcome Measures

Primary Outcomes (1)

• Maximal Tolerated Dose (MTD) of Selinexor

  MTD / Recommended Phase II Dose (RP2D) of selinexor with daunorubicin and cytarabine. Dose Limiting Toxicity (DLT): Non-hematologic - Any grade 3-4 drug-related non-hematologic toxicity, with the following exceptions: Nausea/vomiting or diarrhea adequately controlled with antiemetics/antidiarrheals; Infection or febrile neutropenia adequately controlled with antibiotics; Liver function abnormalities (without clinical symptoms) that recover to baseline or grade 0-1 within 7 days; Grade 3-4 electrolyte or metabolic laboratory abnormalities that are not considered clinically significant by the treating investigator/physician and that recover to baseline or grade 0-1 within 7 days; Alopecia. Hematologic - Grade 3-4 neutropenia and/or thrombocytopenia (thought to be due to marrow hypoplasia and NOT leukemic burden) that does not recover to grade ≤2 by day 56.

  Up to 18 months

Secondary Outcomes (4)

• Rate of Complete Response (CR) Plus Complete Response with Incomplete Count Recovery (CRi).

  Up to 18 months

• Disease Free Survival (DFS)

  Up to 18 months

• Time to Progression (TTP)

  Up to 18 months

• Overall Survival (OS)

  Up to 18 months

Study Arms (1)

Dose Escalation - Selinexor

EXPERIMENTAL

Dose escalation of selinexor with fixed doses of daunorubicin and cytarabine. Induction Therapy may be followed by Consolidation Phase and Maintenance Phase as outlined in the Detailed Description and Intervention Descriptions.

Drug: Selinexor; Drug: Daunorubicin; Drug: Cytarabine

Interventions

Selinexor DRUG

Induction: Oral selinexor on days 1, 3, 8, 10, 15 and 17. * Dose Level 2: 80 mg twice weekly. * Dose Level 1 (starting dose): 60 mg twice weekly. * Dose Level -1: 40 mg twice weekly. Consolidation: Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Maintenance: Selinexor at the same dose as induction on days 1 and 8 a 21 day cycle. They will continue for a maximum of 12 months.

Also known as: KPT-330, SINE KPT-330

Dose Escalation - Selinexor

Daunorubicin DRUG

Induction: Daunorubicin 60 mg/m\^2/day (days 1-3). Consolidation: Daunorubicin 45 mg/m\^2/day (days 1-2).

Also known as: Cerubidine®, daunomycin cerubidine, daunorubicin hydrochloride

Dose Escalation - Selinexor

Cytarabine DRUG

Induction: Cytarabine 100 mg/m\^2/day (days 1-7). Consolidation: Cytarabine 100 mg/m\^2/day (continuous infusion on days 1-5).

Also known as: Cytosar-U, Tarabine PFS, ARA-C

Dose Escalation - Selinexor

Eligibility Criteria

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

You may qualify if:

• Potential participants must have newly diagnosed, previously untreated acute myeloid leukemia (AML) (excluding M3); Must have adverse-risk AML defined as poor-risk karyotype (complex, monosomal or other known poor risk cytogenetic abnormality), poor-risk mutations/fusion genes or known history of antecedent hematologic disorder, or treatment related AML, or be ≥60 years of age; Cytogenetics, FISH or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment.
• May not have undergone any prior therapy for their AML other than hydroxyurea. However, if patients had an antecedent myelodysplastic syndrome (MDS), prior treatment with a hypomethylating agent or any other therapy (with the exception of allogeneic stem cell transplant) used to treat their MDS is allowed.
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of greater than 2 months
• Must have normal organ function
• Able and willing to adhere to the study visit schedule and other protocol requirements
• Baseline left ventricular ejection fraction (LVEF) ≥ 50%
• Women of child-bearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU)mL) within 10 days and again within 24 hours prior to beginning study treatment. Participants of childbearing potential must practice recommended contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Breastfeeding mothers must agree to discontinue nursing if the mother is treated with selinexor.
• Ability to understand and the willingness to sign a written informed consent document
• Able to swallow capsules and have no evidence of GI tract abnormality that would alter the absorption of oral medications
• Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 x upper limit of normal (ULN)

You may not qualify if:

• May not be receiving any other investigational agents
• Documented central nervous system (CNS) involvement of AML
• AML with favorable risk cytogenetic abnormalities including t(15;17), t(8;21) or inv(16)
• Potential participants who are in the blast phase of chronic myeloid leukemia
• Major surgery within 2 weeks of first dose of study drug; must have recovered from the effects of any surgery performed greater than 2 weeks prior
• White blood cell (WBC) count ≥50,000 on hydroxyurea
• Predicted inability to tolerate standard induction chemotherapy with daunorubicin and cytarabine
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• HIV-positive, receiving combination anti-retroviral therapy
• No other malignancies in addition to AML that are currently requiring treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
• History of allogeneic stem cell transplant for MDS or any other antecedent hematologic disorder.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Chromosome Aberrations

Interventions

selinexor; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kendra Sweet, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: March 31, 2015
• Study Start: June 18, 2015
• Primary Completion: September 13, 2016
• Study Completion: February 1, 2021
• Last Updated: October 3, 2022

Record last verified: 2022-09

Locations

US (1)