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

May 4, 2022 updated by: Xiao-Ning Gao, Beijing 302 Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xiao-ning Gao
  • Phone Number: +861066947169
  • Email: gaoxn@263.net

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.
  2. The toxic and side effects caused by the last treatment should be recovered.
  3. Eastern Cooperative Oncology Group score of 0 to 3 points.

  4. 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.
  5. Karnofsky≥70.
  6. The expected survival period is at least 12 weeks.
  7. Non-pregnant, non-breastfeeding women.

Exclusion Criteria:

  1. Suffering from other untreated or unrelieved malignant tumors within 2 years.
  2. Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
  3. 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.
  4. Patients who are unwilling or unable to comply with the protocol.
  5. Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
  6. Women who are pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing 302 Hospital

Investigators

  • Principal Investigator: Xiao-ning Gao, Chinese PLA General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

May 1, 2022

Primary Completion (ANTICIPATED)

April 30, 2023

Study Completion (ANTICIPATED)

April 30, 2024

Study Registration Dates

First Submitted

April 20, 2022

First Submitted That Met QC Criteria

May 4, 2022

First Posted (ACTUAL)

May 5, 2022

Study Record Updates

Last Update Posted (ACTUAL)

May 5, 2022

Last Update Submitted That Met QC Criteria

May 4, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VAA-RR&MRD2022V1.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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