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

7 mars 2022 mis à jour par: Chen Suning, The First Affiliated Hospital of Soochow University

A Multi-center, Phase II, Single-arm Clinical Study of Venetoclax Combined With Azacytiside in the Treatment of Myelodysplastic/Myeloproliferative Neoplasms in Adults

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.

Aperçu de l'étude

Statut

Inscription sur invitation

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Anticipé)

33

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Chine
    • Jiangsu
      • Suzhou, Jiangsu, Chine, 215000
        • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Male or female, Age (years) >= 18；

  2. 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.

  3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;
  4. Liver function: Total bilirubin ≤3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≤3 ULN; alanine aminotransferase (ALT)≤3 ULN；
  5. Renal function#Ccr ≥30 ml/min;
  6. 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:

  1. Acute myeloid leukemia
  2. Myelodysplastic syndrome
  3. Subjects who had previously been treated with Venetoclax
  4. Subjects who are known to be allergic to ingredients of the study drug or their analogues
  5. HIV infection
  6. HBV-DNA or HCV-RNA positive
  7. Subjects with grade 2 or above cardiac failure and those considered unsuitable for inclusion by the investigator
  8. Subjects who are pregnant or breastfeeding
  9. Subjects reject to participate in the study

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: 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.
Autres noms:
  • combination of venetoclax plus azacitidine

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Response Rate (ORR)
Délai: 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.

  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.
Study start date to study end date, or death, whichever comes first, up to 4 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Complete remission rate
Délai: Study start date to study end date, or death, whichever comes first, up to 4 years
  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.
Study start date to study end date, or death, whichever comes first, up to 4 years
Complete remission rate of bone marrow morphology
Délai: 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.
Study start date to study end date, or death, whichever comes first, up to 4 years
Hematology improvement (HI) rate
Délai: 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)

  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.
Study start date to study end date, or death, whichever comes first, up to 4 years
Complete cytogenetic remission rate
Délai: 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.
Study start date to study end date, or death, whichever comes first, up to 4 years
Incidence of severe infection (≥grade 3 )
Délai: Study start date to study end date, or death, whichever comes first, up to 4 years
Assessed using CTCAE 5
Study start date to study end date, or death, whichever comes first, up to 4 years
Spleen response rate
Délai: 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.
Study start date to study end date, or death, whichever comes first, up to 4 years
Symptom response rate
Délai: 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.
Study start date to study end date, or death, whichever comes first, up to 4 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

The First Affiliated Hospital of Soochow University

Les enquêteurs

  • Chercheur principal: Suning Chen, Professor, The First Affiliated Hospital of Soochow University

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Anticipé)

1 avril 2022

Achèvement primaire (Anticipé)

1 août 2022

Achèvement de l'étude (Anticipé)

1 février 2023

Dates d'inscription aux études

Première soumission

21 février 2022

Première soumission répondant aux critères de contrôle qualité

7 mars 2022

Première publication (Réel)

16 mars 2022

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

16 mars 2022

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 mars 2022

Dernière vérification

1 mars 2022

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MDS/MPN-01

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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