RECRUITING

Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm

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Conditions

Recurrent Acute Myeloid LeukemiaRecurrent Chronic Myelomonocytic LeukemiaRecurrent Myelodysplastic/Myeloproliferative NeoplasmRefractory Acute Myeloid LeukemiaRefractory Chronic Myelomonocytic LeukemiaRefractory Myelodysplastic/Myeloproliferative Neoplasm

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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

This phase I/II trial studies the side effects and best dose of gilteritinib and to see how well it works in combination with azacitidine and venetoclax in treating patients with FLT3-mutation positive acute myeloid leukemia, chronic myelomonocytic leukemia, or high-risk myelodysplastic syndrome/myeloproliferative neoplasm that has come back (recurrent) or has not responded to treatment (refractory). Drugs used in chemotherapy, such as 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. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine, venetoclax, and gilteritinib may work better compared to azacitidine and venetoclax alone in treating patients with acute myeloid leukemia, chronic myelomonocytic leukemia, or myelodysplastic syndrome/myeloproliferative neoplasm.

Official Title

A Phase I/II Study of Azacitidine, Venetoclax, and Gilteritinib for Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome With an Activating FLT3 Mutation

Quick Facts

Study Start:2019-12-17
Study Completion:2025-09-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04140487

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. * Diagnosis:
  2. * Phase I cohort: Adults ≥ 18 years with relapsed/refractory FLT3-mutated AML or CMML or other MDS/MPN that is intermediate-2 or high-risk by the International Prognostic Scoring System
  3. * Phase II cohort A: Adults ≥ 18 years with newly diagnosed FLT3-mutated AML
  4. * Phase II cohort B: Adults ≥ 18 years with relapsed/refractory FLT3-mutated AML or CMML or other MDS/MPN that is intermediate-2 or high-risk by the International Prognostic Scoring System
  5. * For all cohorts, patients with either FLT3-internal tandem duplication (FLT3-ITD) or FLT3 D835 mutations will be eligible
  6. * Performance status ≤ 3 (Eastern Cooperative Oncology Group \[ECOG\] scale)
  7. * Total serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
  8. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3 x ULN, unless due to the underlying leukemia approved by the PI
  9. * Creatinine clearance ≥ 30 mL/min
  10. * Ability to swallow
  11. * Signed informed consent
  1. * Prior therapies:
  2. * Phase I cohort: No restriction based on prior therapies
  3. * Phase II cohort A: Patients with prior therapy for AML are not eligible. Prior therapy for antecedent hematologic disorder is allowed. Prior hydroxyurea or cytarabine given for purposes of cytoreduction is also allowed. Prior all trans-retinoic acid given for presumed acute promyelocytic leukemia is also allowed
  4. * Phase II cohort B: No restriction on number of prior therapies
  5. * Patients suitable for and willing to receive intensive induction chemotherapy (for Phase II cohort A only)
  6. * Congenital long QT syndrome or corrected QT interval by Fridericia (QTcF) \> 450 msec. Repeat electrocardiograms (EKGs) after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria. In cases where QTcF \> 450 msec is considered to be falsely increased due to inaccurate automated reading and not clinically significant (e.g. due to bundle branch block), patients are still eligible if cardiologist reviews and documents that QTcF is ≤ 450 msec when manually measured
  7. * Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
  8. * Active grade III-V cardiac failure as defined by the New York Heart Association criteria
  9. * Active central nervous system leukemia
  10. * Known human immunodeficiency virus (HIV) seropositive
  11. * Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection
  12. * Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load
  13. * Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
  14. * Consumed strong inducer of cytochrome P450, family 3, subfamily A (CYP3A) or p-glycoprotein within 3 days of study enrollment. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John's wort
  15. * Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea and/or cytarabine (given for cytoreduction) permitted
  16. * Pregnant women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception throughout the study period and for at least 6 months after the last dose of study drugs. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control throughout the study period and for at least 4 months after the last dose of study drugs. Lactating women (or those planning to breastfeed) should not breastfeed during treatment of gilteritinib and for at least 2 months after the last dose of gilteritinib

Contacts and Locations

Study Contact

Nicholas Short
CONTACT
713-563-4485
nshort@mdanderson.org

Principal Investigator

Nicholas Short
PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

  • Nicholas Short, PRINCIPAL_INVESTIGATOR, M.D. Anderson 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 Date2019-12-17
Study Completion Date2025-09-01

Study Record Updates

Study Start Date2019-12-17
Study Completion Date2025-09-01

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Acute Myeloid Leukemia
  • Recurrent Chronic Myelomonocytic Leukemia
  • Recurrent Myelodysplastic/Myeloproliferative Neoplasm
  • Refractory Acute Myeloid Leukemia
  • Refractory Chronic Myelomonocytic Leukemia
  • Refractory Myelodysplastic/Myeloproliferative Neoplasm