Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

NCT03661307 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0394NCI-2018-01789
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies how well quizartinib, decitabine, and venetoclax work in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome that is untreated or has come back (relapsed). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine and venetoclax, 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. Giving quizartinib and decitabine may work better at treating acute myeloid leukemia and myelodysplastic syndrome.

Conditions

Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose of the combination drugs (Phase I)

  Up to 28 days

• Incidence of adverse events (Phase II)

  Within 3 months

• Overall response rate (ORR) including CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) + partial remission (PR) (Phase II)

  Within 3 months

Study Arms (1)

Treatment (decitabine, quizartinib, venetoclax)

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days 1-10, quizartinib PO every day beginning on day 1 of cycle 1, and venetoclax PO on days 1-14 (days 1-21 if persistent leukemia). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Decitabine; Drug: Quizartinib; Drug: Venetoclax

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, quizartinib, venetoclax)

Quizartinib DRUG

Given PO

Also known as: AC-220, AC010220, AC220

Treatment (decitabine, quizartinib, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (decitabine, quizartinib, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of 1) AML (World Health Organization \[WHO\] classification definition of \>= 20% blasts) excluding acute promyelocytic leukemia (APL) or 2) MDS with \> 10% blasts (defined by the International Prognostic Scoring System \[IPSS\] classification).
• For frontline Cohort: Patients aged \>= 60 years old who are not candidates for intensive induction therapy and agree to receive the proposed combination therapy will be enrolled.
• Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER:
• years of age OR
• \< 75 years of age with at least 1 of the following:
• Poor performance status (Eastern Cooperative Oncology Group \[ECOG\]) score of 2-3.
• Clinically significant heart or lung comorbidities, as reflected by at least 1 of:
• Left ventricular ejection fraction (LVEF) =\< 50%.
• Lung diffusing capacity for carbon monoxide (DLCO) =\< 65% of expected.
• Forced expiratory volume in 1 second (FEV1) =\< 65% of expected.
• Chronic stable angina or congestive heart failure controlled with medication.
• Liver transaminases \> 3 x upper limit of normal (ULN).
• Other contraindication(s) to anthracycline therapy (must be documented).
• Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the principal investigator (PI).
• Patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations equal or younger than 60 year old

You may not qualify if:

• Patients with known allergy or hypersensitivity to quizartinib, mannitol, decitabine or any of their components.
• Prior quizartinib use.
• Patients with known uncontrolled CNS leukemia.
• Only for frontline cohort: patients who are fit for intensive chemotherapy.
• Patients with electrolyte abnormalities at study entry defined as follows: Serum potassium \< 3.5 mEq/L despite supplementation, or \> 5.5 mEq/L Serum magnesium above or below the institutional normal limit despite adequate management. Serum calcium (corrected for albumin levels) above or below institutional normal limit despite adequate management.
• Patients with known significant impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of quizartinib.
• Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study. Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
• Patients with a known human immunodeficiency virus (HIV) infection.
• Patients with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to HBV \[i.e., hepatitis B surface antigen \[HBs Ag\]-, and anti-HBs+\] may participate.
• Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Patients who have had any major surgical procedure within 14 days of day 1.
• Impaired cardiac function including any of the following: Screening ECG with a Fridericia's correction formula (QTcF) \> 450 msec. The QTcF interval will be calculated by Fridericia's correction factor (QTcF). The QTcF will be derived from the average QTcF in triplicate. Patients are excluded if they have QTcF \>= 450. Subjects with prolonged QTcF interval in the setting of RBBB (right bundle branch block) may participate upon review and approval by the medical monitor. RBBB for patients' triplicate EKGs can show false corrected QT (QTc) prolongation; therefore, the Cardiology collaborator for this study will manually review to provide an accurate reading of the QTc. Patients with congenital long QT syndrome. History or presence of sustained ventricular tachycardia requiring medical intervention. Any history of clinically significant ventricular fibrillation or torsades de pointes. Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker). Sustained heart rate of \< 50/minute on pre-entry ECG. Right bundle branch block + left anterior hemiblock (bifascicular block). Complete left bundle branch block. Patients with myocardial infarction or unstable angina within 6 months prior to starting study drug. Congestive heart failure (CHF) New York (NY) Heart Association class III or IV. Atrial fibrillation documented within 2 weeks prior to first dose of study drug. Patients who are actively taking a strong CYP3A4 inducing medication.
• Patients who require treatment with concomitant drugs that prolong QT/QTc interval or strong CYP3A4 inhibitors with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject or if the Investigator believes that beginning therapy with a potentially QTc-prolonging medication (such as anti-emetic except for prochlorperazine) is vital to an individual subject's care while on study.
• Known family history of congenital long QT syndrome.
• Patients who are on strong CYP3A4 inhibitor will be excluded.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Daiichi Sankyo: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Decitabine; Injections; quizartinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

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; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Musa Yilmaz

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Musa Yilmaz

CONTACT

713-745-9945; myilmaz@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 7, 2018
• Study Start: October 31, 2018
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)