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

NCT05362942 | Unknown Phase 2

• 1 other identifier: VAA-RR&MRD2022V1.0
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Minimal Residual Disease

Keywords

Venetoclax; Hypomethylation agent; Cytarabine

Outcome Measures

Primary Outcomes (3)

• Complete remission rate

  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

  Percentage of subjects with MRD negative or MRD \< 0.01%

  At the end of Cycle 2 (each cycle is 28 days)

• MRD Response Rate

  Percentage of subjects with MRD \< 0.1% detectable by multicolor flow cytometry

  At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcomes (4)

• Relapse-Free Survival

  24 months

• Overall Survival

  24 months

• Duration of response

  24 months

• Adverse events

  start of treatment to 2 weeks after end of treatment

Study Arms (1)

venetoclax + Hypomethylation agent + low-dose cytarabine treatment group

EXPERIMENTAL

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

Drug: Venetoclax, Decitabine, Azacytidine, Cytarabine

Interventions

Venetoclax, Decitabine, Azacytidine, Cytarabine DRUG

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.

Also known as: Venetoclax (ABT-199, GDC-0199), Decitabine (Dacogen, 5-aza-2-deoxycytidine), Azacitidine (5-Azacytidine, Ladakamycin), Cytarabine (Cytarabine hydrochloride)

venetoclax + Hypomethylation agent + low-dose cytarabine treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Related Publications (9)

• Burnett AK. Acute myeloid leukemia: treatment of adults under 60 years. Rev Clin Exp Hematol. 2002 Mar;6(1):26-45; discussion 86-7. doi: 10.1046/j.1468-0734.2002.00058.x.

  PMID: 12060482 BACKGROUND

• Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Lowenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. doi: 10.1200/JCO.2005.06.027. Epub 2005 Jan 4.

  PMID: 15632409 BACKGROUND

• Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011 Feb 10;29(5):487-94. doi: 10.1200/JCO.2010.30.1820. Epub 2011 Jan 10.

  PMID: 21220605 BACKGROUND

• Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss O, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. doi: 10.1200/JCO.2013.52.8562. Epub 2014 May 19.

  PMID: 24841975 BACKGROUND

• DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.

  PMID: 30361262 BACKGROUND

• Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 May 20;37(15):1277-1284. doi: 10.1200/JCO.18.01600. Epub 2019 Mar 20.

  PMID: 30892988 BACKGROUND

• DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Dohner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hajek R, Porkka K, Illes A, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.

  PMID: 32786187 BACKGROUND

• Bewersdorf JP, Giri S, Wang R, Williams RT, Tallman MS, Zeidan AM, Stahl M. Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and meta-analysis. Haematologica. 2020 Nov 1;105(11):2659-2663. doi: 10.3324/haematol.2019.242826. No abstract available.

  PMID: 33131256 BACKGROUND

• Qin T, Youssef EM, Jelinek J, Chen R, Yang AS, Garcia-Manero G, Issa JP. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin Cancer Res. 2007 Jul 15;13(14):4225-32. doi: 10.1158/1078-0432.CCR-06-2762.

  PMID: 17634552 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

venetoclax; Decitabine; Azacitidine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides

Study Officials

• Xiao-ning Gao

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao-ning Gao

CONTACT

+861066947169; gaoxn@263.net

Lei Xu

CONTACT

+861066947174; xulei800@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: May 5, 2022
• Study Start: May 1, 2022
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2024
• Last Updated: May 5, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share