Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy for Acute Myeloid Leukemia

Sponsor

Beijing 302 Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05362942

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Although studies are ongoing to evaluate the efficiency and safety of venetoclax-based therapy, alone or in combination with hypomethylation agent or low-dose cytarabine, in relapsed/refractory acute myeloid leukemia, data are scarce and heterogenous. In this study, the investigators aimed to assess safety and response to a new venetoclax-based triple-drug combination regimen (venetoclax + hypomethylation agent + low-dose cytarabine) in acute myeloid leukemia patients who had relapsed/refractory disease or positive minimal residual disease.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Minimal Residual Disease	Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine	Phase 2

Detailed Description

Although the promising activity of venetoclax-based therapy is well demonstrated in the treatment of previously untreated elderly or unfit patients with acute myeloid leukemia, there are few data on the efficacy of venetoclax-based salvage therapy in relapsed/refractory patients, which can be difficult to treat. To date, data on venetoclax as monotherapy or in combination with hypomethylation agent or low-dose cytarabine as a salvage regimen in relapsed/refractory AML are scarce and heterogenous. In this study, the investigators aimed to assess safety and efficiency of a new triple-drug combination regimen, venetoclax + hypomethylation agent + low-dose cytarabine, in patients with relapsed/refractory acute myeloid leukemia or persistent positive minimal residual disease in the salvage setting.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Study of Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy in Patients With Acute Myeloid Leukemia Who Had Relapsed/Refractory Disease or Positive Minimal Residual Disease

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: venetoclax + Hypomethylation agent + low-dose cytarabine treatment group patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine	Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days. Other Names: Venetoclax (ABT-199, GDC-0199) Decitabine (Dacogen, 5-aza-2-deoxycytidine) Azacitidine (5-Azacytidine, Ladakamycin) Cytarabine (Cytarabine hydrochloride)

Arm

Intervention/Treatment

Experimental: venetoclax + Hypomethylation agent + low-dose cytarabine treatment group

patients treated with venetoclax combined with decitabine/azacytidine and low-dose cytarabine

Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine

Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days.

Other Names:

Venetoclax (ABT-199, GDC-0199)

Decitabine (Dacogen, 5-aza-2-deoxycytidine)

Azacitidine (5-Azacytidine, Ladakamycin)

Cytarabine (Cytarabine hydrochloride)

Outcome Measures

Primary Outcome Measures

Complete remission rate [At the end of Cycle 2 (each cycle is 28 days)]
percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)
Complete minimal residual disease (MRD) Response Rate [At the end of Cycle 2 (each cycle is 28 days)]
Percentage of subjects with MRD negative or MRD < 0.01%
MRD Response Rate [At the end of Cycle 2 (each cycle is 28 days)]
Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry

Secondary Outcome Measures

Relapse-Free Survival [24 months]
Time interval from leukemia free state to the first recurrence or death
Overall Survival [24 months]
Time interval from start of treatment until death or last follow-up
Duration of response [24 months]
Time interval from morphologic/MRD response to loss of response or death
Adverse events [start of treatment to 2 weeks after end of treatment]
Number of subjects with adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged ≥18 years old, voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures.
The toxic and side effects caused by the last treatment should be recovered.
Eastern Cooperative Oncology Group score of 0 to 3 points.
The organ function is intact.

Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (Upper Limit of Normal).
Creatinine≤1.5×ULN.
Bilirubin≤1.5×ULN.

Karnofsky≥70.
The expected survival period is at least 12 weeks.
Non-pregnant, non-breastfeeding women.

Exclusion Criteria:

Suffering from other untreated or unrelieved malignant tumors within 2 years.
Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association [NYHA] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial.
Patients who are unwilling or unable to comply with the protocol.
Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
Women who are pregnant or breastfeeding.