Clinical Study of Venetoclax Combined With Azacytiside in the Treatment of Myelodysplastic/Myeloproliferative Neoplasms in Adults
Study Details
Study Description
Brief Summary
To explore the efficacy of venetoclax combined with azacytidine in Myelodysplastic / myeloproliferative neoplasms（MDS/MPN）, so as to improve the overall survival and treatment status of MDS/MPN patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
At present, there is no standardized treatment strategy for MDS/MPN. The purpose of our study is to explore the efficacy of venetoclax combined with azacytidine in the treatment of MDS/MPN, so as to improve the overall survival and treatment status of patients with MDS/MPN. After the participants were treated with four cycles of venetoclax combined with azacytidine, the efficacy was evaluated according to the 2015 adult MDS/MPN response criteria to determine the disease status. Participants with disease progression and intolerance withdrew from the study during treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment regime On day 1 of each cycle, decitabine 75 mg/m2 will be given subcutaneously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 14 day cycle is finished. |
Drug: venetoclax combined with azacitidine
On day 1 of each cycle, decitabine 75 mg/m2 will be given subcutaneously, and will continue for 5 days. Simultaneously the patient will start out with Venetoclax 100mg and progress to 400mg until the 14 day cycle is finished.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [Study start date to study end date, or death, whichever comes first, up to 4 years]
ORR (equals the rates of complete remission [CR]+partial remission [PR]+complete cytogenetic remission [CCyR]+marrow response [MR[+clinical benefit [CB] )of venetoclax in combination with azacitidine. CR and CCyR are shown in the secondary outcome measures below. PR: Normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts (and blast equivalents) reduced by 50%, but remaining>5% of cellularity except in cases of MDS/MPN with≤5% bone marrow blasts at baseline. MR: Optimal marrow response: Presence of all marrow criteria necessary for CR without normalization of peripheral blood indices. Partial marrow response: Bone marrow blasts (and blast equivalents) reduced by 50%, but remaining>5% of cellularity, or reduction in grading of reticulin fibrosis from baseline on at least 2 bone marrow evaluations spaced at least 2 months apart. CB: Hematology improvement, spleen response and symptom response.
Secondary Outcome Measures
- Complete remission rate [Study start date to study end date, or death, whichever comes first, up to 4 years]
Bone marrow: ≤5% myeloblasts (including monocytic blast equivalent in case of CMML) with normal maturation of all cell lines and return to normal cellularity Osteomyelofibrosis absent or equal to "mild reticulin fibrosis" (≤grade 1 fibrosis). Peripheral blood: Leukocyte≤10×10E9 cells/L; Hemoglobin≥11g/dL; Platelets≥100×10E9/L, ≤450×10E9/L; Neutrophils≥1.0×10E9/L; Blasts 0%; Neutrophil precursors reduced to≤2%; Monocytes ≤1.0× 10E9/L. Extramedullary disease: Complete resolution of extramedullary disease present before therapy (eg, cutaneous disease, disease-related serous effusions), including palpable hepatosplenomegaly.
- Complete remission rate of bone marrow morphology [Study start date to study end date, or death, whichever comes first, up to 4 years]
Presence of all marrow criteria necessary for CR without normalization of peripheral blood indices as presented above.
- Hematology improvement (HI) rate [Study start date to study end date, or death, whichever comes first, up to 4 years]
Percentages of participants with HI (erythroid/platelet/neutrophil responses) Erythroid response: Hemoglobin increase by≥2.0 g/dL; Transfusion independence (TI) for ≥8 week for patients requiring at least 4 packed red blood cell transfusions in the previous 8 week; Only red blood cell transfusions given based on physician's judgment for a pretreatment Hgb of ≤8.5 g/dL will count in the red blood cell TI response evaluation. Platelet response: TI when previously requiring platelet transfusions of at least a rate of 4 platelet transfusions in the previous 8 week; Pretreatment≤20×10E9/L: increase from<20×10E9/L to>20×10E9/L and by at least 100%; Pretreatment>20×10E9/L but≤100×10E9/L: absolute increase of ≥30×10E9/L. Neutrophil response: Pretreatment≤0.5×10E9/L at least 100% increase and an absolute increase≥0.5×10E9/L; Pretreatment>0.5×10E9/L and≤1.0×10E9/L, at least 50% increase and an absolute increase ≥0.5×10E9/L.
- Complete cytogenetic remission rate [Study start date to study end date, or death, whichever comes first, up to 4 years]
Resolution of previously present chromosomal abnormality (known to be associated with myelodysplastic, syndrome myeloproliferative neoplasms, or MDS/MPN), as seen on classic karyotyping with minimal of 20 metaphases or FISH.
- Incidence of severe infection (≥grade 3 ) [Study start date to study end date, or death, whichever comes first, up to 4 years]
Assessed using CTCAE 5
- Spleen response rate [Study start date to study end date, or death, whichever comes first, up to 4 years]
Either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not palpable.
- Symptom response rate [Study start date to study end date, or death, whichever comes first, up to 4 years]
Improvement in symptoms as noted by decrease of ≥50% as per the MPN-SAF TSS scoring<20 were not considered eligible for measuring clinical benefit.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female, Age (years) >= 18；
-
Patients newly diagnosed or previously treated with MDS/MPNs (CMML, MDS/MPN-U, aCML) according to 2016 WHO diagnostic criteria:
Initial diagnosis: CMML: CPSS-mol intermediate risk 2 and above; aCML; MDS/MPN-U.
Previous treatment: HMA treatment failed.
-
Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
-
Liver function: Total bilirubin ≤3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≤3 ULN; alanine aminotransferase (ALT)≤3 ULN；
-
Renal function#Ccr ≥30 ml/min;
-
Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.
Exclusion Criteria:
-
Acute myeloid leukemia
-
Myelodysplastic syndrome
-
Subjects who had previously been treated with Venetoclax
-
Subjects who are known to be allergic to ingredients of the study drug or their analogues
-
HIV infection
-
HBV-DNA or HCV-RNA positive
-
Subjects with grade 2 or above cardiac failure and those considered unsuitable for inclusion by the investigator
-
Subjects who are pregnant or breastfeeding
-
Subjects reject to participate in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology | Suzhou | Jiangsu | China | 215000 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
Investigators
- Principal Investigator: Suning Chen, Professor, The First Affiliated Hospital of Soochow University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDS/MPN-01