- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05805072
Selinexor and HAAG With/Without HMA in Relapsed/Refractory Acute Leukemia (AML) Patients
An Open Label, Single Arm, Single-Center Exploratory Study to Evaluate the Efficacy and Safety of Selinexor and HAAG +/- HMA in Relapsed/Refractory Acute Leukemia (AML) Patients
Study Overview
Status
Conditions
Detailed Description
This protocol corresponds to a single-center, open-label, single-arm, exploratory study designed to determine the efficacy and safety of the combination of selinexor with HAAG +/- HMA in patients with relapsed or refractory AML. The patients who respond to this combination treatment will undergo allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment according to patient's wishes.
Each cycle of treatment will compromise 2 weeks of selinexor treatment, and at least two weeks off treatment. The new cycle will not start if there is an ongoing grade 3 or higher non-hematologic toxicity or persistent grade 3 neutropenia in patients achieving CR.
Study design allows 20 patients. Treatment will consist of selinexor 60 mg/day orally on d1,4,8,11, HHT 1 mg/day intravenously on days 3 to 9, cytarabine 10 mg/m2 q12h, intravenously on days 3 to 9, aclacinomycin 10 mg/day intravenously on days 3 to 6, G-CSF 50-600 mcg/m2/day intravenously from days 2 to start, this dosage will be adjusted according to the hemogram, DAC 20 mg/m2/day intravenously on days 1 to 5. Whether to add hypomethylating agents was decided by the investigator according to the patient's disease degree and tolerance status. If patients had previously been exposed to decitabine, azacitidine will added this regimen, AZA 20 mg/m2/day subcutaneously on days 1 to 7.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Jiangsu
-
Suzhou, Jiangsu, China, 215006
- The First Affiliated Hospital of Soochow University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women aged ≥18 years.
- Diagnosis of AML (defined according to the 5th of the World Health Organization [WHO] 2022 criteria) of any type except for acute promyelocytic leukemia (APL; AML M3)and the following conditions were met: Relapsing or refractory AML
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use two reliable methods of contraception for six months after their last dose of medication.
- Patients whose expecting survival time will be more than 3 months.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
Exclusion Criteria:
- AML transformed from chronic myeloid leukemia.
- Patients with APL/AML M3.
- Presence of CNS leukemia.
- Uncontrolled infection or other serious disease.
- Unstable cardiovascular function: Cardiac ejection fraction (EF)<0.5, or congestive heart failure (CHF) of NYHA Class ≥ 2.
- Unstable Liver and kidney function:TBLL≥2.0 mg/dl, AST≥3×ULN, Ccr≥50 ml/min, SpO2<92%.
- Known human immunodeficiency virus (HIV) infection.
- Active hepatitis B or hepatitis C infection.
- Pregnant and lactating women. Patients with other commodities that the investigators considered not suitable for the enrollment.
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+HAAG±HMA
|
Selinexor 60 mg/day, orally on d1,4,8,11
Homoharringtonine 1 mg/day intravenously on days 3 to 9
cytarabine 10 mg/m2 q12h, intravenously on days 3 to 9
aclacinomycin 10 mg/day intravenously on days 3 to 6
granulocyte colony-stimulating factor 50-600 mcg/m2/day intravenously from days 2 to start, this dosage will be adjusted according to the hemogram,
Decitabine 20 mg/m2/day intravenously on days 1 to 5.
Azacitidine 20 mg/m2/day subcutaneously on days 1 to 7
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With CR/CRi
Time Frame: End of cycle 1 and 2 (each cycle is 28 days)
|
Number of Participants With CR/CRi CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease. CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L |
End of cycle 1 and 2 (each cycle is 28 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Time from registration to event, max 2 years
|
Overall survival (OS) was calculated from the date of informed consent to the date of death.
Patients still alive at the end of follow-up were censored at the last date of follow-up.
|
Time from registration to event, max 2 years
|
Number of Participants With ORR
Time Frame: End of cycle 1 and 2 (each cycle is 28 days)
|
ORR =CR+CRi+PR+MLFS PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease |
End of cycle 1 and 2 (each cycle is 28 days)
|
Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
Time Frame: 1-2 induction cycles (4 - 8 weeks)
|
Rate of ASCT: Percentage of patients being transplanted after induction therapy (stem cell transplantation)
|
1-2 induction cycles (4 - 8 weeks)
|
Progression-Free Survival
Time Frame: Time from registration to event, max 2 years
|
Progression-free survival (PFS): was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse. Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%. |
Time from registration to event, max 2 years
|
Number of adverse events
Time Frame: End of cycle 1 and 2 (each cycle is 28 days)
|
Adverse events are evaluated with CTCAE V5.0
|
End of cycle 1 and 2 (each cycle is 28 days)
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Adjuvants, Immunologic
- Protein Synthesis Inhibitors
- Antibiotics, Antineoplastic
- Decitabine
- Lenograstim
- Azacitidine
- Cytarabine
- Homoharringtonine
- Aclacinomycins
Other Study ID Numbers
- Selinexor+HAAG+HMA
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Relapsed/Refractory AML
-
Technische Universität DresdenAbbVieActive, not recruitingRelapsed Adult AML | Refractory AMLGermany
-
Samsung Medical CenterMinistry of Health, Republic of KoreaRecruitingRelapsed Pediatric AML | Refractory Pediatric AML | Relapsed Pediatric Solid Tumor | Refractory Pediatric Solid TumorKorea, Republic of
-
Apollomics Inc.Zhejiang CrownMab Biotech Co. LtdRecruitingRelapsed/Refractory AMLChina
-
Apollomics Inc.Zhejiang CrownMab Biotech Co. LtdRecruitingRelapsed/Refractory AMLChina
-
Fujian Medical UniversityUnknown
-
Clavis PharmaSyneos Health; Theradex; CardiaBase; Learn & ConfirmCompletedRelapsed/Refractory AMLUnited Kingdom, Spain
-
Shanghai General Hospital, Shanghai Jiao Tong University...Recruiting
-
Seattle Children's HospitalChildren's Healthcare of Atlanta; Pediatric Oncology Experimental Therapeutics...CompletedAML | Acute Leukemia of Ambiguous Lineage | ALL | Relapsed/Refractory AML | Relapsed/Refractory ALL | Secondary AML/MDSUnited States, Canada
-
The Affiliated Hospital of the Chinese Academy...Chinese PLA General HospitalUnknown
Clinical Trials on Selinexor
-
Karyopharm Therapeutics IncBelgium and Luxembourg Gynaecological Oncology Group; North-Eastern German... and other collaboratorsActive, not recruitingEndometrial CancerUnited States, China, Israel, Spain, Belgium, Germany, Greece, Czechia, Italy, Canada
-
Memorial Sloan Kettering Cancer CenterRecruitingSolid Tumor | Rhabdoid Tumor | Wilms Tumor | Nephroblastoma | Malignant Peripheral Nerve Sheath Tumors | MPNST | XPO1 Gene MutationUnited States
-
The First Hospital of Jilin UniversityRecruitingPTCL Patients Who Achieved Complete Response From Frontline TreatmentChina
-
University of RochesterKaryopharm Therapeutics IncRecruitingSmoldering Multiple MyelomaUnited States
-
Karyopharm Therapeutics IncGOG Foundation; European Network of Gynaecological Oncological Trial Groups... and other collaboratorsRecruitingEndometrial CancerUnited States, Belgium, Spain, Israel, Australia, Italy, Georgia, Ireland, Greece, Slovakia, Canada, Hungary, Czechia
-
University of UtahKaryopharm Therapeutics IncActive, not recruitingPrimary Myelofibrosis | Post-polycythemia Vera Myelofibrosis | Post-essential Thrombocythemia MyelofibrosisUnited States
-
Karyopharm Therapeutics IncCompletedHematological MalignanciesUnited States, Denmark, Canada
-
Karyopharm Therapeutics IncTerminatedRichter's TransformationUnited States, Germany, United Kingdom, Spain, Poland
-
Morten Mau-SoerensenHospices Civils de Lyon; Gustave Roussy, Cancer Campus, Grand Paris; Institut... and other collaboratorsUnknownThymoma | Advanced Thymic Epithelial TumourDenmark, France
-
Chunrui LiNanjing IASO Biotherapeutics Co.,LtdRecruitingExtramedullary Multiple MyelomaChina