Acute Myeloid LeukemiaPhase 2NCT04146038
Salsalate, Venetoclax, and Decitabine or Azacitidine for the Treatment of Acute Myeloid Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
A Phase 2 study testing Azacitidine, Decitabine and Salsalate in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myeloblasts 10 Percent or More of Bone Marrow Nucleated Cells
- What is being tested?
- Azacitidine, Decitabine and Salsalate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Oct 2020to 25 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
Official title: Salsalate + Venetoclax/Decitabine for Patients With Acute Myelogenous Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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
- Being tested
- Azacitidine, Decitabine, Salsalate, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV
DecitabineDrug
Also called 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine
Given IV
SalsalateDrug
Also called Disalcid, Mono-Gesic, o-Salicylsalicylic Acid, Salflex
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Azacitidine; Drug: Decitabine; Drug: Salsalate; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine
Study drug associated adverse events during therapy
Measured: During the first 2 cycles, 56 days total
Secondary outcomes (1)
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
Measured: During the first 2 cycles 56 days total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2019
- Study start26 Oct 2020
- Primary completion25 Oct 2021
- Study completion25 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Rutgers, The State University of New JerseyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Roger Strair, MD, PhD, Rutgers, The State University of New Jersey
- Investigators
- Roger K Strair, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04146038
- Sponsor's protocol ID
- 021905
- Other IDs
- NCI-2019-07031, Pro2019001209, Pro2019001209, P30CA072720
- Status last verified
- Apr 2023
- First submitted
- 29 Oct 2019
- Last updated
- 24 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Salsalate + Venetoclax/Decitabine for Patients With Acute Myelogenous Leukemia or Advanced Myelodysplasia/Myeloproliferative Disease
- ClinicalTrials.gov ID
- NCT04146038
- Acronym / sponsor ID
- 021905
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Oct 2020 (actual)
- Primary completion
- 25 Oct 2021 (actual)
- Study completion
- 25 Oct 2022 (actual)
- First posted
- 31 Oct 2019 (actual)
- Results
- Posted 24 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (salsalate, decitabine, azacitidine, venetoclax) | Experimental | Drug: Azacitidine, Drug: Decitabine, Drug: Salsalate, Drug: VenetoclaxCYCLE 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV | Drug | Treatment (salsalate, decitabine, azacitidine, venetoclax) |
| DecitabineAlso: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, DeoxyazacytidineGiven IV | Drug | Treatment (salsalate, decitabine, azacitidine, venetoclax) |
| SalsalateAlso: Disalcid, Mono-Gesic, o-Salicylsalicylic Acid, SalflexGiven PO | Drug | Treatment (salsalate, decitabine, azacitidine, venetoclax) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (salsalate, decitabine, azacitidine, venetoclax) |
Primary outcome
Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine
Time frame: During the first 2 cycles, 56 days total
Study drug associated adverse events during therapy
1 secondary outcome
Number of Participants With Complete or Partial Response
Time frame: During the first 2 cycles 56 days total
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger K Strair principal investigator
Rutgers Cancer Institute of New Jersey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine, Decitabine and Salsalate in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by Rutgers, The State University of New Jersey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Adverse Events Incidence With of Salicylate + Venetoclax + Decitabine (time frame: During the first 2 cycles, 56 days total). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.