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

An Exploratory Clinical Study of Selinexor Combined With Venetoclax and Azactidine in the Treatment of Acute Myeloid Leukemia Patients Who Are Not Eligible for Intense Chemotherapy Regimen at Initial Treatment

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia, Adult
• Intervention / Treatment: Drug: Selinexor; Drug: Venetoclax; Drug: Azacitidine

Detailed Description

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. In this stage, three dosage groups were set up, namely 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 regimen was repeated every 28 days. In this case, RP2D is determined based on MTD, safety, and all other data.

The methods of venetoclax and azacitidine remain unchanged during consolidation therapy. Before RP2D is determined, the dosage of selinexor is determined by the researchers based on individual subject tolerance. After RP2D is determined, the study enters the second stage of dose expansion. 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.

The subjects will participate in the screening period, treatment period, and follow-up period. The screening period lasts for a maximum of 28 days before medication. The treatment period lasts from the first day of the first cycle to the end of the study treatment. The follow-up period starts after the end of treatment and lasts for at least 12 months.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. 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.
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.
4. Renal function meets the following criteria: creatinine clearance rate ≥ 30 mL/min (Cockroft-Gault formula).
5. Expected survival time greater than 6 months

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: selinexor venetoclax Azacitidine; 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; three dosage groups were set up, selinexor 60mg QW, 40mg BIW, or 60mg BIW; Other Names: XPO1-i; Drug: Venetoclax; cycle 1 100mg d1 200mg d2 400mg d3-28 cycle 2-4 400mg d1-d28; Other Names: BCL-2i; Drug: Azacitidine; 75mg/m2 d1-d7 28d/cycle 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D of selinexor in this study	from the first day to the last day of the cycle	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD negative rate	MRD negative rate at the end of 2 cycles and 4 cycles of induction therapy	up to 16 weeks
Compound complete response rate	From first dose of treatment to first day response is documented by evaluation	up to 16 weeks
The time to compound complete response	From first dose of treatment to first day response is documented by evaluation	up to 16 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Actual): March 30, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Venetoclax; Azacitidine
• Other Study ID Numbers: IIT2022053

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes