RECRUITING

5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies

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Conditions

Myelodysplastic SyndromesMDS/MPN Crossover Syndromes

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Another term for myelodysplastic syndrome is bone marrow failure. The bone marrow is where components of blood such as red cells, platelets and white cells are made. In bone marrow failure, the ability for bone marrow to make these cells is decreased. In myelodysplastic syndrome, this decreased bone marrow function is believed to result from abnormalities that prevent the normal maturation process by which bone marrow cells develop into red blood cells, white blood cells and platelets. In myelodysplastic syndrome, these abnormal bone marrow cells occupy space in the bone marrow and prevent the function of remaining normal bone marrow cells. One approach to treating the abnormal growth of immature 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. Both 5-azacitidine (5AZA) and decitabine (DEC) are FDA-approved to treat MDS. In this study, 5AZA and DEC will be administered using an alternating low doses schedule in an attempt to overcome the known mechanisms of resistance to the administration of 5AZA or DEC as single agents caused by automatic adaptive shifts in DNA metabolism.

Official Title

Proof-Of-Concept Study of Metabolically Optimized, Non-Cytotoxic 5-Azacitidine and Decitabine Epigenetic Therapy for Myeloid Malignancies

Quick Facts

Study Start:2020-11-16
Study Completion:2026-12-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04187703

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Participants must have MDS or MDS/myeloproliferative overlap disorder with potential sensitivity to HMA therapy, defined as prior published evidence of response to HMA
  2. * Myelodysplastic Syndromes:
  3. * As classified by hematopathology review of WHO categories, myelodysplastic/myeloproliferative neoplasm unclassifiable, refractory anemia with ring sideroblasts and thrombocytosis, refractory cytopenia with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS), refractory cytopenia with multi-lineage dysplasia (RCMD), refractory anemia with excess blasts (RAEB), myelodysplastic syndrome with isolated del(5q), myelodysplastic syndrome unclassifiable (MDS-U).
  4. * Participant with MDS who are IPSS-R high and very high risk or IPSS intermediate 2 risk and higher are excluded given proven overall survival benefit in higher risk MDS from AZA-001 with this treatment
  5. * Myelodysplastic/myeloproliferative neoplasm overlap disorders ---MDS/MPN crossover syndromes with limited evidence of extramedullary hematopoiesis (may not have palpable splenomegaly) and reticulin fibrosis of grade 1 or less without evidence of progression to accelerated phase. These may include but may not be limited to RARS-T, CMML, Atypical CML (BCR-ABL negative), and MDS/MPN NOS
  6. * Indication for HMA therapy: Symptomatic anemia OR thrombocytopenia with a platelet count of \<100 x 109/L OR transfusion dependence for red-cells OR transfusion dependence for platelets OR absolute neutrophil count \< 1.0 x 109/L
  7. * Participants must have performance status of 60% or greater by Karnofsky Performance Status (KPS)
  8. * Must have adequate end organ function defined as:
  9. * AST and ALT \< 3× the upper limit of normal (ULN)
  10. * Bilirubin ≤ 1.5× the ULN. 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
  11. * As azacitidine and decitabine have little renal metabolism, and have proven safety even in dialysis participants, renal function is not an inclusion or exclusion criteria
  12. * Subjects must have the ability to understand and the willingness to sign a written informed consent document and complete study related procedures.
  1. * MDS with IPSS-R high or very high risk, or IPSS intermediate-2 or high risk disease
  2. * Prior Treatment with azacitidine, decitabine or investigational HMA therapy with overlapping mechanism of action (e.g. guadecitibine)
  3. * No other disease directed therapy, save for hydroxyurea, including experimental or investigational drug therapy for 14 days prior to study entry.
  4. * Toxicity (grade 2 or higher) from prior therapies including chemotherapy, targeted therapy, immunotherapy, experimental therapy, radiation or surgery must be resolved to grade 1 or less.
  5. * Currently pregnant or breast-feeding. Females of child bearing (FOCBP) potential 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)
  6. * Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to:
  7. * Ongoing or active infection. As participants with MDS and MDS/MPNs are prone to infections, if participants are actively being treated with appropriate antibiotics or antifungal therapy with clinical evidence of infection control, then they will be considered eligible for study.
  8. * Uncontrolled concurrent malignancy
  9. * Congestive heart failure of NYHA class III/IV. Participants with compensated heart failure are permitted.
  10. * Unstable angina pectoris
  11. * New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
  12. * Decompensated liver cirrhosis (Child-Pugh score ≥12 or a MELD score ≥21)
  13. * Psychiatric illness/social situations that would limit compliance with study requirements.
  14. * Any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the participant or impair the assessment of study results.
  15. * 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
  16. * Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of 5AZA-alt-DEC.
  17. * Participants with known active HIV infection, as this will further increase the risk for opportunistic infections. However, participants with chronic HIV with undetectable viral load by PCR, without opportunistic infection, and on a stable regimen of antiretroviral therapy would be eligible.
  18. * Known allergy or hypersensitivity to any component of azacitidine or decitabine formulations

Contacts and Locations

Study Contact

Benjamin Tomlinson, MD
CONTACT
216-844-0139
benjamin.tomlinson@uhhospitals.org

Principal Investigator

Benjamin H Tomlinson, Tomlinson
PRINCIPAL_INVESTIGATOR
Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Locations (Sites)

Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
United States

Collaborators and Investigators

Sponsor: Benjamin Tomlinson

  • Benjamin H Tomlinson, Tomlinson, PRINCIPAL_INVESTIGATOR, Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-16
Study Completion Date2026-12-01

Study Record Updates

Study Start Date2020-11-16
Study Completion Date2026-12-01

Terms related to this study

Additional Relevant MeSH Terms

  • Myelodysplastic Syndromes
  • MDS/MPN Crossover Syndromes