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

Primary Purpose

Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myeloblasts 10 Percent or More of Bone Marrow Nucleated Cells

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Azacitidine
Decitabine
Salsalate
Venetoclax
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Rutgers Cancer Institute of New Jersey

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (salsalate, decitabine, azacitidine, venetoclax)

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine
Study drug associated adverse events during therapy

Secondary Outcome Measures

Number of Participants With Complete or Partial Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Full Information

First Posted
October 29, 2019
Last Updated
April 28, 2023
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04146038
Brief Title
Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
Official Title
Salsalate + Venetoclax/Decitabine for Patients With Acute Myelogenous Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 26, 2020 (Actual)
Primary Completion Date
October 25, 2021 (Actual)
Study Completion Date
October 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the tolerability of the addition of standard dose salsalate to the standard treatment combination of venetoclax + hypomethylating agent (HMA) (decitabine or azacitidine [5-azacytidine]). SECONDARY OBJECTIVES: I. Determine the remission rate and, when feasible, perform exploratory studies of: Ia. Patterns of mutation clearance. Ib. Distribution of cells with low and high reactive oxygen species (ROS) content at various points during therapy. OUTLINE: CYCLE 1: Patients receive salsalate orally (PO) twice daily (BID) until completion of cycle 1. 24-48 hours later or concurrent with salsalate, patients begin to receive decitabine intravenously (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (salsalate, decitabine, azacitidine, venetoclax)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Salsalate
Other Intervention Name(s)
Disalcid, Mono-Gesic, o-Salicylsalicylic Acid, Salflex, Salicylsalicylic Acid, Salsitab
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine
Description
Study drug associated adverse events during therapy
Time Frame
During the first 2 cycles, 56 days total
Secondary Outcome Measure Information:
Title
Number of Participants With Complete or Partial Response
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
During the first 2 cycles 56 days total

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger K Strair
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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