Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

Acute Myeloid Leukemia Clinical Trial

Official title:

A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03701308
• Other study ID #: NCI-2018-02130
• Secondary ID: NCI-2018-02130A0
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: March 28, 2019
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II/III trial studies how well daunorubicin and cytarabine with or without uproleselan works in treating older adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. Drugs used in chemotherapy, such as daunorubicin 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. Uproleselan may prevent cancer from returning or getting worse. Giving daunorubicin and cytarabine with uproleselan may work better in treating patients with acute myeloid leukemia compared to daunorubicin and cytarabine alone.

Description:

PRIMARY OBJECTIVES:

I. Compare the event-free survival (EFS) of daunorubicin, cytarabine plus uproleselan versus daunorubicin and cytarabine in subjects >= age 60 with previously untreated acute myeloid leukemia. (Phase II) II. Compare the overall survival (OS) of the daunorubicin, cytarabine plus uproleselan to daunorubicin and cytarabine in this patient population. (Phase III)

SECONDARY OBJECTIVES:

I. Determine the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), complete remission with incomplete hematopoietic recovery (CRh) and cytogenetic complete remission (CCyR) for each chemotherapy regimen.

II. Determine the overall survival (OS), and remission duration of patients for each chemotherapy regimen.

III. Describe the frequency and severity of adverse events for patients for each chemotherapy regimen.

IV. Describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

CORRELATIVE SCIENCE OBJECTIVES:

I. Correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters and with response rates, response duration, survival and cure in patients treated with various induction and post-induction regimens.

II. Correlate specific karyotype groups with selected molecular abnormalities and with measurable residual disease.

III. To determine karyotype changes at end of consolidation and the influence of the type of change (or no change) in karyotype at the end of consolidation on subsequent clinical course.

IV. To determine karyotype changes at relapse and the influence of the type of change (or no change) in karyotype at relapse on subsequent clinical course.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: INDUCTION: Patients receive daunorubicin intravenously (IV) on days 1-3 and cytarabine via continuous intravenous infusion (CIVI) over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-3 and cytarabine CIVI over 12 hours on days 1-5.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.

CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months in year 2, and then every 6 months for up to 5 years.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 670
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of acute myeloid leukemia (AML) based on 2017 World Health Organization (WHO) criteria excluding acute promyelocytic leukemia with PML-RARA.

• Note: Patients with myeloid sarcoma without bone marrow involvement, acute leukemia of ambiguous lineage or blast transformation of chronic myelogenous leukemia (CML) are not eligible.

• No activating mutation in the Fms-like tyrosine kinase-3 (FLT3) defined as a ratio of mutant to wild-type allele >= 0.05 by capillary electrophoresis or a variant allele fraction of >= 5% by next generation sequencing from either bone marrow or peripheral blood.

• No evidence of CNS involvement of AML.

• No prior chemotherapy for myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or AML including hypomethylating agents (e.g. azacitidine and decitabine), ruxolitinib or lenalidomide with the following exceptions:

• Emergency leukapheresis.

• Hydroxyurea.

• Growth factor/cytokine support.

• All-trans retinoic acid (ATRA).

• Single dose of intrathecal cytarabine and/or methotrexate for patients undergoing lumbar puncture to evaluate for CNS involvement.

• Total bilirubin =< 3 x upper limit of normal (ULN)

• Creatinine < 3 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min/1.73m^2

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Cytarabine
Given IV
• Daunorubicin
Given IV
• Uproleselan
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center	Adrian	Michigan
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Saint Alphonsus Cancer Care Center-Baker City	Baker City	Oregon
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Community Cancer Institute	Clovis	California
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	East Carolina University	Greenville	North Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Saint Peter's Community Hospital	Helena	Montana
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	North Shore University Hospital	Manhasset	New York
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Mount Sinai Hospital	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Saint Alphonsus Cancer Care Center-Ontario	Ontario	Oregon
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Kootenai Clinic Cancer Services - Sandpoint	Sandpoint	Idaho
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Overlook Hospital	Summit	New Jersey
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Wake Forest Baptist Health - Wilkes Medical Center	Wilkesboro	North Carolina
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS) (Phase II)	EFS is defined as the time from the date of randomization to the first of failure to achieve a complete remission (CR)/ CR with incomplete blood count recovery (CRi) during induction, relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.	Up to 5 years
Primary	Overall survival (OS) (Phase III)	Will be measured from the date of randomization to death from any cause, with patients last known to be alive censored at the date of last contact.	Up to 5 years
Secondary	EFS rate	Will be formally tested hierarchically in a confirmatory setting at an overall one sided alpha of 0.025 level at the same time as the primary endpoint. Both hazard ratio and p-value for EFS will be presented.	Up to 1 year
Secondary	Impact of off-protocol transplantation	Sensitivity analyses will be conducted. In addition, the proportion of patients who received transplantation in the two arms will be summarized and compared using a chi-square test.	Up to 5 years
Secondary	Consistency of the treatment effect among each subgroup	Non-parametric methods such as Kaplan-Meier and log-rank tests will be used within each subgroup. Univariate/multivariate Cox models will be fit within each subgroups; hazard ratios will be used to quantify the treatment effect within each subgroup, along with the 95% confidence intervals.	From baseline up to 5 years
Secondary	Disease-free survival (DFS)		Time from achieving a complete response to time of relapse or death, assessed up to 5 years
Secondary	Complete remission (CR) and overall response rate		Up to 5 years
Secondary	Incidence of adverse events	Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.	Up to 5 years
Secondary	Prediction of CR, EFS, DFS, and OS by pretreatment characteristics such as age, morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status with clinical outcomes	The associations between these baseline factors and CR, EFS, DFS, and OS will be analyzed using Kaplan-Meier curves, log-rank test, contingency table and chi-square test whenever appropriate. Multivariable analysis including Cox proportional hazards models and logistic regression models will be used as well to evaluate the associations.	Up to 5 years