Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease

NCT04146038 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 021905NCI-2019-07031Pro2019001209P30CA072720
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects of salsalate when added to venetoclax and decitabine or azacitidine in treating patients with acute myeloid leukemia or myelodysplasia/myeloproliferative disease that has spread to other places in the body (advanced). Drugs used in chemotherapy, such as salsalate, venetoclax, decitabine, and azacitidine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myeloblasts 10 Percent or More of Bone Marrow Nucleated Cells; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine

  Study drug associated adverse events during therapy

  During the first 2 cycles, 56 days total

Secondary Outcomes (1)

• Number of Participants With Complete or Partial Response

  During the first 2 cycles 56 days total

Study Arms (1)

Treatment (salsalate, decitabine, azacitidine, venetoclax)

EXPERIMENTAL

CYCLE 1: Patients receive salsalate PO BID until completion of cycle 1. 24-48 hours later or concurrent with salsalate, patients begin to receive decitabine IV for 10 days or azacitidine IV for 7 days. Starting 24 hour after salsalate, patients also receive venetoclax PO continuously until completion of cycle 1. CYCLE 2: Patients receive decitabine IV for 5 days or azacitidine IV for 7 days, salsalate PO BID, and venetoclax PO continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Decitabine; Drug: Salsalate; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (salsalate, decitabine, azacitidine, venetoclax)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (salsalate, decitabine, azacitidine, venetoclax)

Salsalate DRUG

Given PO

Also known as: Disalcid, Mono-Gesic, o-Salicylsalicylic Acid, Salflex, Salicylsalicylic Acid, Salsitab

Treatment (salsalate, decitabine, azacitidine, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (salsalate, decitabine, azacitidine, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Histologically proven acute myelogenous leukemia (AML) or advanced myeloid malignancy \[myelodysplasia; chronic myelomonocytic leukemia (CMML); or chronic myeloproliferative disease (MPD) each with \>= 10% myeloblasts in blood or bone marrow\]
• For patients with de novo AML: must not be a candidate for standard induction therapy based upon age, co-morbidities, patient choice, high risk features known to have poor outcomes with standard induction therapy (ELN high risk disease by cytogenetics, deoxyribonucleic acid \[DNA\] mutation profile or TP53 mutation)
• Patients with advanced myelodysplastic syndrome (MDS), secondary AML, relapsed/refractory AML, prior hypomethylating agent are eligible
• Patients must give informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin \< 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional ULN
• Creatinine \< 2 mg/dL

You may not qualify if:

• White blood cell (WBC) uncontrolled (\> 15,000/uL) despite hydroxyurea or cytarabine x 3 days. Known central nervous system (CNS) AML
• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient?s ability to complete the study, at the discretion of the investigator. Pregnant patients are excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Salsalate or other agents used in the study. Examples include aspirin
• The effects of venetoclax and decitabine or 5-azacytidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 24 weeks after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, therefore, known human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with treatment medications or other agents administered during the study

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

Azacitidine; Decitabine; Injections; salicylsalicylic acid; Sodium Salicylate; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; 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; Drug Administration Routes; Drug Therapy; Therapeutics; Salicylic Acid; Salicylates; Hydroxybenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Results Point of Contact

• Title: Roger K. Strair, MD, PhD
• Organization: Cancer Institute of New Jersey Rutgers

strairrk@cinj.rutgers.edu

732-235-4523

Study Officials

• Roger K Strair

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Professor of Medicine, Chief of Hematologic Malignancies Medical Oncology

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: October 31, 2019
• Study Start: October 26, 2020
• Primary Completion: October 25, 2021
• Study Completion: October 25, 2022
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)