Metabolically Optimized, Non-cytotoxic Low Dose Weekly Decitabine/Venetoclax in MDS and AML

NCT05184842 | Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 2021-13466
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 3

Brief Summary

Myeloid malignancies which include AML (acute myeloid leukemia) and MDS (myelodysplatic syndrome) are cancers of the bone marrow which lead to bone marrow failure. The bone marrow is the place or factory in the body where components of blood such as red cells, platelets and white cells are made. In bone marrow failure, the ability of the bone marrow to make these cells is decreased. The decreased bone marrow function is the result from abnormalities that develop in the malignant cells which prevent the normal maturation process by which bone marrow cells develop into red blood cells, white blood cells and platelets. The malignant cells in the bone marrow are not good at maturing to make the components of the blood that you need, they occupy space in the bone marrow and prevent the function of remaining normal bone marrow cells. DNA is a chemical substance within cells that stores information needed for cell growth and cell behavior. One approach to treating the malignant cells is to give chemotherapy which damages DNA within these cells and causes their death. Unfortunately, such therapy has side-effects, since even normal cells can be affected by the treatment. Decitabine is FDA approved for treatment of MDS and AML. Venetoclax is approved for AML in combination with Azacitidine for patients with AML or are over age 75 or unfit for chemotherapy. In this study, Decitabine and venetoclax will be administered using a low dose weekly schedule in an attempt to improve efficacy by decreasing the side effects often seen when these drugs are given at standard dosing.

Conditions

Myelodysplastic Syndromes; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Are Able to Continue on Treatment Without Dose Interruptions or Delays

  The percentage of participants who are able to continue on treatment without dose interruptions or delays was defined as not having to delay or interrupt treatment due to toxicity or intolerability for more than two weeks during the 12-week induction period.

  Up to 12 weeks

Secondary Outcomes (6)

• Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Hematologic Recovery (CRi)

  Up to 3 months

• Event-free Survival (EFS)

  Up to 12 months

• Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)

  3 months

• Post Baseline Transfusion Independence Rate

  Up to 12 months

• Rate of Hospitalization

  Up to 12 months

Study Arms (1)

Decitabine/Venetoclax (Single Arm)

EXPERIMENTAL

Administration: Decitabine is reconstituted with 5 ml sterile water to facilitate subcutaneous administration. Decitaboine is given by subcutaneous injection. Venetoclax is taken as a tablet prepared by patients pharmacy. Venetoclax is given at a dose of 400 mg po once per week concurrently with the Decitabine dose (+/- 1 day allowed ).

Drug: Venetoclax; Drug: Decitabine

Interventions

Venetoclax DRUG

Venetoclax 400 mg po on days 1, 8, 15 and 22 of each cycle (28-day cycle)

Decitabine/Venetoclax (Single Arm)

Decitabine DRUG

Decitabine 0.2 mg/kg subcutaneous (SQ) on days 2, 9, 16, 23 (for aggressive disease will add decitabine on days 3, 10, 17, 24)

Decitabine/Venetoclax (Single Arm)

Eligibility Criteria

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

You may qualify if:

• Patient must have a diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with a histopathologic diagnosis confirmed by hematopathology review
• Indication for therapy with potential sensitivity to hypomethylating agents (HMA) therapy, defined as prior published evidence of response to HMA
• Patients must be 18 years of age or older
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3
• Patients must have adequate end organ function defined as.
• Aspartate aminotransferase (AST) and Alanine transaminase (ALT) \< 4× the upper limit of normal (ULN)
• Bilirubin ≤ 2× the ULN (upper limit of normal). If elevated bilirubin is due to impaired conjugation (e.g., Gilbert's disease or concomitant medication) or disease related hemolysis, then direct bilirubin ≤ 1.5× the ULN
• As decitabine and venetoclax have little renal metabolism, and have proven safety even in dialysis patients, renal function with a creatinine clearance ≥30 mL/min or on dialysis is allowed
• Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures.

You may not qualify if:

• Acute promyelocytic leukemia (APL)
• Core binding factor AML who are candidates for chemotherapy
• Prior Treatment with azacitidine, decitabine or venetoclax
• No other disease directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry
• Currently pregnant or breast-feeding. Females of childbearing potential (FOCBP) must have negative serum pregnancy test within 72 hours from treatment start. (NOTE: FOCBP is any biologic female, regardless of sexual or gender orientation, having undergone tubal ligation, or remaining celibate by choice, who has not undergone a documented hysterectomy or bilateral oophorectomy or has had a menses any time in the preceding 12 months (therefore not naturally post-menopausal for \> 12 months)
• Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to:
• Ongoing or active infection. As patients with myeloid malignancies are prone to infections, if patients are actively being treated with appropriate antibiotics or antifungal therapy with clinical evidence of infection control, then they will be considered eligible for study.
• Uncontrolled concurrent malignancy
• Congestive heart failure of xNew York Heart Association (NYHA) class III/IV. Patients with compensated heart failure are permitted
• Unstable angina pectoris
• New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
• Decompensated liver cirrhosis (Child-Pugh score ≥12 or a Model for Enst-Stage Liver Disease (MELD) score ≥21
• Psychiatric illness/social situations that would limit compliance with study requirements
• Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results
• Women of Child-Bearing Potential (WOCBP) and males that are unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control; abstinence, condom) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Servier: collaborator
• The V Foundation for Cancer Research: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (3)

University of California Davis Health (UC Davis Health)

Sacramento, California, 95817, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

White Plains Hospital

White Plains, New York, 10601, United States

RECRUITING

Related Publications (1)

• Goldfinger M, Mantzaris I, Shastri A, Saunthararajah Y, Gritsman K, Sica RA, Kornblum N, Shah N, Levitz D, Rockwell B, Shapiro LC, Gupta R, Pradhan K, Xue X, Munoz A, Dhawan A, Fehn K, Comas M, Verceles JA, Jonas BA, Kambhampati S, Shi Y, Braunschweig I, Cooper DL, Konopleva M, Feldman EJ, Verma A. A weekly low-dose regimen of decitabine and venetoclax is efficacious and less myelotoxic in a racially diverse cohort. Blood. 2024 Nov 28;144(22):2360-2363. doi: 10.1182/blood.2024025834.

  PMID: 39316768 DERIVED

MeSH Terms

Conditions

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

Interventions

venetoclax; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mendel Goldfinger, MD
• Organization: Montefiore Medical Center

mgoldfin@montefiore.org

718-920-4826

Study Officials

• Mendel Goldfinger, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mendel Goldfinger, MD

CONTACT

718-920-4826; mgoldfin@montefiore.org

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: SPONSOR

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: January 11, 2022
• Study Start: March 23, 2022
• Primary Completion: December 20, 2023
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 5, 2026
• Results First Posted: August 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)