Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Older Patients With Acute Myeloid Leukemia (AML) in Complete Remission

Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) in Complete Remission

This phase 2, open label, non-randomized study will evaluate the safety of administering high dose cytarabine (HiDAC) consolidation therapy on days 1-3 of each cycle, as compared to standard administration on days 1, 3, and 5 of each cycle, in patients 61 years and older with de novo acute myeloid leukemia (AML).

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: Cytarabine

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Teresa Ware, MPH; Phone Number: 352-273-5739; Email: PMO@cancer.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Both males and females ≥ 61 years of age
• A clinical diagnosis of de novo, non-M3 acute myeloid leukemia (AML) confirmed by greater than 20% blasts in peripheral blood or on diagnostic bone marrow biopsy who have completed intensive induction chemotherapy and are confirmed in complete remission #1 (defined by < 5% myeloblasts on recovery bone marrow biopsy, Absolute neutrophil count > 1000/uL and platelets > 100x103/uL) and able to receive HiDAC consolidation #1
• Patients on the prospective arm must be willing to have labs/clinic visits at UF Health Shands approximately every 48 hours +/- 24 hours after discharge from chemotherapy admission to be included. If prospective subjects cannot be followed at the UF site then telephone visits are allowed to follow for toxicity and transfusions. Records can be requested from subject's local physician office.
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures. For subjects on the historical arm, there will be a waiver of informed consent (as these patients may be deceased or not be available for retrospective consent).

Exclusion Criteria:

• Age < 61 years
• Patients unable to provide informed consent for prospective arm
• Secondary AML (documented history of antecedent hematological disorder, such as myelodysplastic syndrome or therapy-related AML) or chronic myeloid leukemia (CML) in blast crisis
• Patients receiving, received, or who will receive a FLT3 inhibitor
• Patients receiving, received, or who will receive an IDH1 or IDH2 inhibitor
• Serum creatinine greater than 2 mg/dL
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
• For historical arm, subjects will be excluded if adequate data is not available in electronic medical record (e.g., if patient was followed by their local oncologist between chemotherapy cycles and labs/transfusions/clinic notes, etc. are not available)
• Karnofsky performance status of 40 or less at study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospective HiDAC Treatment (HiDAC 123); Subject on this arm will be treated with HiDAC prospectively.	Drug: Cytarabine; Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.; Other Names: Ara-C; Cytosar; cytosine arabinoside; Drug: Cytarabine; Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles.; Other Names: Ara-C; Cytosar; cytosine arabinoside
Other: Historical HiDAC Treatment (HiDAC 135); Subjects on this arm will be historical controls who have previously received treatment with HiDAC.	Drug: Cytarabine; Subjects on this arm will prospectively receive consolidation therapy with cytarabine. Subjects will be treated with 1000 mg/m2 cytarabine intravenously every 12 hours on Days 1-3 of each consolidation cycle. Subjects will receive up to four consolidation cycles.; Other Names: Ara-C; Cytosar; cytosine arabinoside; Drug: Cytarabine; Subjects on this arm will have received consolidation therapy with cytarabine between 2/1/2017 and 2/1/2019. Subjects will have received 1000 mg/m2 cytarabine intravenously every 12 hours on days 1, 3, and 5 of each consolidation cycle and will have received up to 4 consolidation cycles.; Other Names: Ara-C; Cytosar; cytosine arabinoside

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of neutropenia	Determine the duration of neutropenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of thrombocytopenia	Determine the duration of thrombocytopenia in older patients with de novo AML after consolidation chemotherapy with HiDAC 123, as compared to historical controls treated with HiDAC 135.	5 months
Incidence of documented infections	Compare the incidence of documented infections (bloodstream infection, pneumonia, invasive fungal infection, Clostridium difficile infection, typhlitis, and febrile neutropenia) in patients receiving HiDAC 123 and HiDAC 135.	5 months
Number of transfusions	Compare the number of red blood cell and platelet transfusions per cycle in patients receiving HiDAC 123 and HiDAC 135.	4 months
Readmission rates and length of readmission stay	Compare the incidence of readmission and the length of readmission stay in patients receiving HiDAC 123 and HiDAC 135.	5 months
Non-hematologic toxicities	Compare the differences in non-hematologic toxicities in patients receiving HiDAC 123 and HiDAC 135.	5 months
Time to next treatment	Compare the time to next treatment (next chemotherapy cycle, transplant, etc.) in patients receiving HiDAC 123 and HiDAC 135.	5 months

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Jack Hsu, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2022
• Primary Completion (Actual): January 12, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: elderly; bone marrow; acute myeloid leukemia; high dose cytarabine; HiDAC; consolidation; chemotherapy schedule
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: UF-HEM-009; IRB202003214 (Other Identifier: University of Florida); OCR40160 (Other Identifier: University of Florida)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No