Reduced Intensive Idarubicin and Cytarabine Plus Venetoclax as First-line Treatment for Adults AML and MDS

A Multi-center Prospective Single Arm Clinical Study of Reduced Intensive 3 + 5 Idarubicin and Cytarabine Chemotherapy Plus Venetoclax as First-line Treatment for Adults With Acute Myeloid Leukaemia and High-risk Myelodysplastic Syndrome

Reduced intensive 3 + 5 idarubicin and cytarabine chemotherapy plus venetoclax as first-line treatment for adults with acute myeloid leukaemia and high-risk myelodysplastic syndrome

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Drug: idarubicin; Drug: Cytarabine

Detailed Description

Multiple clinical trials about chemotherapy plus venetoclax in primary diagnosed AML or relapsed/refractly AML were ongoing to attempt the facility of the combination. Zu et al demostrated that full dose of 3 + 7 daunorubicin and cytarabine chemotherapy plus 8 days escalated venetoclax acheived 91% of CR/CRi with 97% 1-year overall survival and 72% 1-year event-free survival. In this trial , we try to reduced the intensive of 3 + 5 idarubicin and cytarabine chemotherapy, but prolong venetoclax to two weeks in the induction therapy in adults AML/MDS. We expect to increase the induced remission rate by extending the dosage of targeted drug venetoclax, and minimize the side effects by reducing the dose of 3 + 7 induction chemotherapy, so as to achieve the goal of high efficiency and low toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weiyan Zheng, MD; Phone Number: 86-13857187088; Email: zhengwy2015@163.com
• Study Contact Backup: Name: Xuepin Luo, MD; Phone Number: 86-15167157190; Email: luoxp1603@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. aged 18-60 years
2. had a confirmed diagnosis of previously untreated de novo acute myeloid leukaemia or high risk myelodysplastic syndrome by bone marrow examination according to the criteria presented by WHO.
3. Eastern Cooperative Oncology Group performance status of 0-2.
4. adequate renal and hepatic function (appendix 2 p 45), and left ventricular ejection fraction of at least 45% by echocardiography.

Exclusion Criteria:

1. younger than 18 years old, or older than 60 years old.
2. Diagnosed as acute promyelocytic leukaemia.
3. Pretreated with anthracycline.
4. CNS involvement.
5. Positive for HIV, hepatitis B virus, or hepatitis C virus.
6. New York Heart Association cardiovascular disability status higher than grade 2 (grade 2 is defined as cardiac disorder that is asymptomatic at rest, but ordinary physical activity might result in fatigue, palpitations, dyspnoea, or angina), chronic respiratory diseases requiring continuous supplementary oxygen, inability to take oral medication or malabsorption syndrome
7. Uncontrollable systemic infection (viral, bacterial, or fungal),
8. Inability to sign the informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group; Reduced intensive of 3 + 5 Idarubicin and Cytarabine plus Venetoclax as induction therapy	Drug: idarubicin; Idarubicin 6mg/m2 d5-7; Other Names: Idamycin; Demethoxydaunorubicin; Drug: Cytarabine; Cytarabine 60mg/m2 d5-9; Other Names: Cytosar; Cytosine arabinoside

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR	assessment of the composite complete remission rate (CR=CR+CRi)	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD	assessment of bone marrow measurable residual disease by flow cytometry	Week 6
EFS	Evaluate the event-free survival	2 years
OS	Evaluated the overall survival	2 years
adverse events	Monitor of adverse events	at any time

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Weiyan Zheng, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): April 2, 2024
• Primary Completion (Estimated): April 2, 2026
• Study Completion (Estimated): April 2, 2027

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 2, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; 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; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Idarubicin
• Other Study ID Numbers: 20230413IAVEN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No