Clinical Study of Venetoclax Combined With Azacytiside in the Treatment of Myelodysplastic/Myeloproliferative Neoplasms in Adults

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• Neoplasms 9,365
• Myeloproliferative Disorders 626
• Myelodysplastic-Myeloproliferative Diseases 231

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's planned enrollment of 33 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Lead sponsor

The First Affiliated Hospital of Soochow University is the lead sponsor of 252 studies on the registry; 148 are open to participants now.

Study arms

• 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

Interventions

• Drugvenetoclax 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.

  Also known as: combination of venetoclax plus azacitidine

Primary outcomes

1. Overall Response Rate (ORR)

   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. 1. CR and CCyR are shown in the secondary outcome measures below. 2. 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. 3. 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. 4. CB: Hematology improvement, spleen response and symptom response.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

Secondary outcomes

1. Complete remission rate

   1. 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). 2. 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. 3. Extramedullary disease: Complete resolution of extramedullary disease present before therapy (eg, cutaneous disease, disease-related serous effusions), including palpable hepatosplenomegaly.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

2. Complete remission rate of bone marrow morphology

   Presence of all marrow criteria necessary for CR without normalization of peripheral blood indices as presented above.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

3. Hematology improvement (HI) rate

   Percentages of participants with HI (erythroid/platelet/neutrophil responses) 1. 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. 2. 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. 3. 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.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

4. Complete cytogenetic remission rate

   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.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

5. Incidence of severe infection (≥grade 3 )

   Assessed using CTCAE 5

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

6. Spleen response rate

   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.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years

7. Symptom response rate

   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.

   Time frame: Study start date to study end date, or death, whichever comes first, up to 4 years