Cladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT04047641 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2017-0153NCI-2019-04730
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and how well cladribine, idarubicin, cytarabine, and quizartinib work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that is newly diagnosed, has come back (relapsed), or does not respond to treatment (refractory). Drugs used in chemotherapy, such as cladribine, idarubicin, and cytarabine, 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. Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving quizartinib with cladribine, idarubicin, and cytarabine may help to control acute myeloid leukemia or high-risk myelodysplastic syndrome.

Conditions

Acute Myeloid Leukemia; Blasts 20 Percent or More of Bone Marrow Nucleated Cells; High Risk Myelodysplastic Syndrome; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Myeloid Leukemia; Recurrent High Risk Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory High Risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Event free survival (EFS)

  Will be estimate using the Kaplan-Meier method for each patient cohort. In addition, efficacy EFS will be analyzed in the intent to treat (ITT) population per cohort.

  From the date of start of treatment until event (resistance or relapse) or death, whichever occurred first, assessed up to 12 months

• Incidence of adverse events

  Defined as any clinically significant treatment-related grade 3 or greater non-hematologic toxicity. Patient toxicity data will be summarized using frequency and percentages, by type, grade and relationship to the study drugs.

  Up to 12 months

Secondary Outcomes (5)

• Overall survival (OS)

  Up to 12 months

• Disease free survival (DFS)

  Up to 12 months

• Rate of response

  Up to 12 months

• Change of FLT3 ligand level

  Baseline up to 12 months

• Change in the presence of other gene mutations

  Baseline up to 12 months

Study Arms (1)

Treatment (idarubicin, cladribine, cytarabine, quizartinib)

EXPERIMENTAL

INDUCTION: Patients receive idarubicin Intravenous over 1 hours on days 1-3, cladribine intravenous over 1-2 hours on days 1-5, cytarabine Intravenous over 3 hours on days 1-5 (or days 1-3 for patients over age 60), and quizartinib by mouth daily on days 6-19. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR or CRp after Induction receive idarubicin Intravenous over 1 hours on days 1-2, cladribine Intravenous over 1-2 hours on days 1-3, cytarabine Intravenous over 3 hours on days 1-3, and quizartinib by mouth daily on days 4-28. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients who achieve CR or CRi/CRh after Consolidation receive quizartinib by mouth daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cladribine; Drug: Cytarabine; Drug: Idarubicin; Drug: Quizartinib

Interventions

Cladribine DRUG

Given Intravenous

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (idarubicin, cladribine, cytarabine, quizartinib)

Cytarabine DRUG

Given Intravenous

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (idarubicin, cladribine, cytarabine, quizartinib)

Idarubicin DRUG

Given Intravenous

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Treatment (idarubicin, cladribine, cytarabine, quizartinib)

Quizartinib DRUG

Given by mouth

Also known as: AC-220, AC010220, AC220

Treatment (idarubicin, cladribine, cytarabine, quizartinib)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of
• AML (World Health Organization \[WHO\] classification definition of \>= 20% blasts, excluding Acute promyelocytic leukemia),
• Acute biphenotypic leukemia or
• High-risk MDS (\> 10% bone marrow blasts)
• Frontline cohort: Patients aged 18 to 65 years
• Relapse cohort: Patients aged \>=18 years old
• Patients may be newly diagnosed (Frontline cohort) or with prior therapy (Relapsed cohort) as follows:
• For frontline cohort: Patients must be chemonaive, i.e., not have received any chemotherapy (except hydroxyurea \[Hydrea\] \[no dose limit\], tretinoin \[atra\] \[no dose limit\] or ara-C \[one or two doses (max 2 gr/m\^2 per dose)\] for transient control of hyperleukocytosis) for AML or MDS. They may have received hypomethylating agents for prior MDS and transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or Hydrea are allowed
• For relapsed cohort: Patients with previously treated, relapsed or refractory AML, acute biphenotypic leukemia or high-risk MDS (\> 10% bone marrow blasts)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Creatinine \< 1.5 mg/dl
• Total bilirubin \< 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder
• Transaminases (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN)
• Potassium, magnesium, and calcium (normalized for albumin) levels should be at least within institutional normal limits
• Ability to take oral medication

You may not qualify if:

• Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
• Breastfeeding women
• Patients with current active malignancies or any remission for \< 6 months, except patients with carcinoma in situ or with non-melanoma skin cancer who may be in remission for less than 6 months or have active disease
• Active clinically serious and uncontrolled infection. Patients with recent infections must have no temperature of \>= 101 degrees Fahrenheit (F) for at least 48 hours (hrs) (before first dose, day 1)
• Patients with known significant impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of quizartinib
• Documented active central nervous system leukemia (patients with history of central nervous system \[CNS\] leukemia without active disease are allowed)
• Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
• Patients who have had any major surgical procedure within 14 days of day 1
• Impaired cardiac function including any of the following:
• Screening electrocardiography (ECG) with a corrected QT (QTc) \> 450 msec. The QTc 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 electrocardiograms (EKGs) can show false 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
• 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)
• Heart rate of \< 50/minute on pre-entry ECG

Sponsors & Collaborators

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

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute

Interventions

Cladribine; Cytarabine; Idarubicin; quizartinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Musa Yilmaz

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Musa Yilmaz

CONTACT

713-794-5783; 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: August 5, 2019
• First Posted: August 7, 2019
• Study Start: October 22, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)