Randomization for the Identification of Best Treatment Intensity for Less Fit Adults With Acute Myeloid Leukemia and Myeloid Neoplasms

NCT07094750 | Not Yet Recruiting

• 2 other identifiers: RG1125566NCI-2025-04530
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial studies whether less fit adults with acute myeloid leukemia (AML) or myeloid neoplasms are willing to let a computer program decide (randomization) whether they receive lower- or higher-intensity chemotherapy. Historically, treatment decision-making for patients with AML or myeloid neoplasms has divided patients into two categories, with patients considered fit receiving intensive "curative" chemotherapy, and patients considered unfit, such as older patients with a higher risk of early death from therapy, receiving non-intensive "palliative" therapy or no therapy. With the introduction of new treatment agents, it has become difficult to determine the difference between intensive and non-intensive therapy, especially for patients considered unfit for whom treatment-related side effects remain a concern. Treatment intensity is best identified through randomized trials but often patients are unwilling to undergo randomization due to preset beliefs. However, with improved supportive care and the awareness that new treatment agents may have similar risks as intensive therapy, it may be possible that more patients are willing to be randomized. This may help identify the best treatment intensity for less fit adults with AML or myeloid neoplasms, which may improve outcomes.

Conditions

Acute Myeloid Leukemia; Myeloid Neoplasm; Acute Leukemia of Ambiguous Lineage

Outcome Measures

Primary Outcomes (1)

• Willingness to randomize (Feasibility)

  Patient willingness to randomize will be indicated on the survey instrument Patient Preference for Treatment Assignment Survey. Patients who select the box indicating "I am willing to let a coin flip (i.e. computer program) decide whether I receive lower- or higher-intensity chemotherapy" will be considered willing to randomize. Will consider randomization feasible (i.e. a subsequent, larger study would be designed as a randomized trial) if the true proportion of patients willing to be randomized is 60% or higher.

  At baseline

Study Arms (4)

Arm I (randomized higher-intensity therapy)

EXPERIMENTAL

Patients receive SOC or investigational higher-intensity therapy on a subsequent treatment trial that is at least as intense as 7+3 regimen at the discretion of the treating physician on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration

Arm II (randomized lower-intensity therapy)

EXPERIMENTAL

Patients receive SOC or investigational lower-intensity therapy on a subsequent treatment trial that is less intense than 5+2 regimen at the discretion of the treating physician on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration

Arm III (patient choice higher-intensity therapy)

ACTIVE COMPARATOR

Patients receive SOC or investigational higher-intensity therapy on a subsequent treatment trial that is at least as intense as 7+3 regimen according to physician/patient preference on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration

Arm IV (patient choice lower-intensity therapy)

ACTIVE COMPARATOR

Patients receive SOC or investigational lower-intensity therapy on a subsequent treatment trial that is less intense than 5+2 regimen according to physician/patient preference on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Collection; Other: Electronic Health Record Review; Other: Questionnaire Administration

Interventions

Bone Marrow Collection PROCEDURE

Undergo bone marrow assessment

Also known as: Collection, Bone Marrow

Arm I (randomized higher-intensity therapy); Arm II (randomized lower-intensity therapy); Arm III (patient choice higher-intensity therapy); Arm IV (patient choice lower-intensity therapy)

Electronic Health Record Review OTHER

Ancillary studies

Arm I (randomized higher-intensity therapy); Arm II (randomized lower-intensity therapy); Arm III (patient choice higher-intensity therapy); Arm IV (patient choice lower-intensity therapy)

Questionnaire Administration OTHER

Ancillary studies

Arm I (randomized higher-intensity therapy); Arm II (randomized lower-intensity therapy); Arm III (patient choice higher-intensity therapy); Arm IV (patient choice lower-intensity therapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (randomized higher-intensity therapy); Arm II (randomized lower-intensity therapy); Arm III (patient choice higher-intensity therapy); Arm IV (patient choice lower-intensity therapy)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Diagnosis of high grade myeloid neoplasm (\> 10% blasts in blood or marrow), other than acute promyelocytic leukemia (APL) according to the 2022 International Consensus Classification (ICC) classification. Patients with acute leukemias of ambiguous lineage are eligible
• The use of cytoreductive therapy before treatment is permitted. Patients with symptoms/signs of leukostasis, white blood cell (WBC) \> 100,000/μL, or acute symptoms that in the opinion of the treating physician are likely related to their high-grade myeloid neoplasm may receive up to 2 doses of cytarabine (up to 500 mg/m\^2 each) prior to study day 1
• Patients may have received treatment for antecedent low-grade myeloid neoplasm (\< 10% myeloid blasts on blood or bone marrow)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3 (for patients aged \< 75 years) or ECOG performance status of 0 - 2 (for patients aged ≥ 75 years)
• The presence of one or more of the following criteria for 'unfitness'. (Patients without respiratory symptoms at rest are eligible and should only complete spirometry/diffusion capacity of the lung for carbon monoxide \[DLCO\] measurements as clinically indicated):
• ECOG Performance Status of 2 or 3
• Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina
• Documented DLCO ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%; or dyspnea at rest, or requiring supplemental oxygen
• Creatinine clearance ≥ 30 mL/min to \< 45 ml/min
• Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN)
• Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy
• Adequate cardiac function:
• Patients aged ≤ 60 years without a history of cardiac disease or evidence of heart failure are eligible if they also exhibit the following:
• Chest x-ray (CXR) without evidence of moderate or severe pulmonary edema or pleural effusion, and a normal cardio-mediastinal silhouette

You may not qualify if:

• Known hypersensitivity to cytarabine, anthracycline, hypomethylating agents, or venetoclax
• Cardiovascular disability status of New York Heart Association class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain
• Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
• Concomitant illness associated with a likely survival of \< 1 year
• Active pregnancy or breast feeding

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Jacob Appelbaum, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Appelbaum, MD, PhD

CONTACT

206-606-4643; jappelb@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 30, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: March 13, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)