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
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Tianjin
-
Tianjin, Tianjin, China
- Institute of Hematology & Blood Diseases Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
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. |
three dosage groups were set up, selinexor 60mg QW, 40mg BIW, or 60mg BIW
Other Names:
cycle 1 100mg d1 200mg d2 400mg d3-28 cycle 2-4 400mg d1-d28
Other Names:
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
Time Frame: 1 year
|
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
Time Frame: up to 16 weeks
|
MRD negative rate at the end of 2 cycles and 4 cycles of induction therapy
|
up to 16 weeks
|
|
Compound complete response rate
Time Frame: up to 16 weeks
|
From first dose of treatment to first day response is documented by evaluation
|
up to 16 weeks
|
|
The time to compound complete response
Time Frame: up to 16 weeks
|
From first dose of treatment to first day response is documented by evaluation
|
up to 16 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IIT2022053
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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