Selinexor、Venetoclax and Azactidine in the Treatment of ND AML Patients Who Are Not Eligible for Intense Chemotherapy

NCT06449482 | Terminated Phase 1 FDA Drug

• 1 other identifier: IIT2022053
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single arm open exploratory clinical trial to evaluate the efficacy and safety of selinexor combined with venetoclax and azacitidine. This study will be divided into two stages: dose increasing stage and dose expanding stage. In the dose-increasing stage, the study induction therapy was designed using a 3+3 design. The induction therapy and consolidation therapy of the subjects will be administered at RP2D doses. During this study period, there were a total of 4 cycles. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy. In addition, if the subject does not achieve remission (CR/Cr or PR) after 2 cycles of consolidation treatment (at the end of the 4th course), the study will be terminated by the subject, and the clinical doctor will choose the subsequent treatment for the subject based on clinical experience.

Conditions

Acute Myeloid Leukemia, Adult

Outcome Measures

Primary Outcomes (1)

• RP2D of selinexor in this study

  from the first day to the last day of the cycle

  1 year

Secondary Outcomes (3)

• MRD negative rate

  up to 16 weeks

• Compound complete response rate

  up to 16 weeks

• The time to compound complete response

  up to 16 weeks

Study Arms (1)

selinexor venetoclax Azacitidine

EXPERIMENTAL

In the dose-increasing stage, the subject induction therapy was designed using a 3+3 design. selinexor 60mg QW, 40mg BIW, or 60mg BIW, in combination with venetoclax 100mg d1 200mg d2 400mg d3-28, orally once a day, and azacitidine 75mg/m2, d1-7, subcutaneously. The medication regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data. During this study period, there were a total of 4 courses. The treatment cycle of the subjects will include 2 cycles of induction therapy and up to 2 cycles of consolidation therapy.

Drug: Selinexor; Drug: Venetoclax; Drug: Azacitidine

Interventions

Selinexor DRUG

three dosage groups were set up, selinexor 60mg QW, 40mg BIW, or 60mg BIW

Also known as: XPO1-i

selinexor venetoclax Azacitidine

Venetoclax DRUG

cycle 1 100mg d1 200mg d2 400mg d3-28 cycle 2-4 400mg d1-d28

Also known as: BCL-2i

selinexor venetoclax Azacitidine

Azacitidine DRUG

75mg/m2 d1-d7 28d/cycle 4 cycles

selinexor venetoclax Azacitidine

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed AML patients diagnosed according to WHO standards who are not suitable for the standard induction treatment regimen of cytarabine combined with anthracycline drugs due to age or comorbidities.
• Age ≥ 75 years old, ECOG score 0-2 points; The patient's age range is 18-75 years old, with an ECOG score of 0-3.
• Liver function meets the following criteria: total bilirubin\<3 × Upper limit of normal range (ULN) (\<75 years old), total bilirubin\<1.5 × ULN (≥ 75 years old), AST\<3 × ULN and ALT\<3 × ULN.
• Renal function meets the following criteria: creatinine clearance rate ≥ 30 mL/min (Cockroft-Gault formula).
• Expected survival time greater than 6 months

You may not qualify if:

• patient who has received BCL2 inhibitors, demethylation drugs, chemotherapy, CAR-T therapy, or other experimental therapies.
• History of myeloproliferative tumors (MPN).
• Cytogenetic low risk, such as t (8; 21), inv (16), t (16; 16) or t (15; 17).
• Acute promyelocytic leukemia.
• AML central nervous system (CNS) involvement.
• Pregnancy or lactation period.
• I underwent major surgery within 4 weeks before the first study medication.
• Subjects with unstable or active cardiovascular diseases who meet any of the following criteria:
• Symptomatic myocardial ischemia;

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

selinexor; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

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

Model Details: selinexor venetoclax and azacitidine

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: June 10, 2024
• Study Start: May 5, 2023
• Primary Completion: March 30, 2025
• Study Completion: March 30, 2025
• Last Updated: May 30, 2025

Record last verified: 2024-03

Locations

CN (1)