Efficacy of Dose-Adjusted Regimen on Survival in Frail Adults With Acute Lymphoblastic Leukemia (EPOCH)

Efficacy on Progression Free Overall Survival of a Dose-Adjusted Regimen in Frail Adult Patients With Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is characterized by the abnormal proliferation of immature precursor cells, disrupting normal hematopoiesis and causing severe anemia and thrombocytopenia due to genetic mutations. Conventional treatment with intensive chemotherapy is limited for elderly patients or those with comorbidities, adversely affecting their survival. In Mexico, alongside a higher incidence, treatment-related complications are more frequent, particularly with drugs such as asparaginase or anthracyclines, which limits therapeutic efficacy. The transition to infusion-based therapies promises to reduce these complications, improve treatment tolerance, and optimize clinical outcomes, marking a significant advancement in the management of this disease. Modifying treatment regimens toward infusion therapies has the potential to significantly reduce adverse complications, enhance treatment tolerance, and ultimately improve clinical outcomes for patients who cannot benefit from conventional intensive regimens. This approach not only aims to optimize treatment effectiveness but also to minimize associated risks, thus representing an important advancement in the management of acute lymphoblastic leukemia in clinical settings such as those in Mexico

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Overall Survival; Acute Lymphobkastic Leukemia
• Intervention / Treatment: Drug: Patients meeting criteria will receive DA-EPOCH via central line for 5 days every 21 days, with monitoring, supportive care, transfusions, prophylaxis, and G-CSF for 5 doses per cycle

Detailed Description

The treatment of acute lymphoblastic leukemia (ALL) in adults represents a therapeutic challenge, particularly in patients with high-risk factors, clinical frailty, or socioeconomic limitations that hinder adherence to intensive outpatient regimens. While protocols such as HyperCVAD have been widely used, their toxicity can be significant in certain subgroups. In this context, the EPOCH regimen has been explored as an inpatient consolidation alternative that allows a gradual transition toward less toxic regimens, with potential benefits in vulnerable populations.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Christian O Ramos, MD; Phone Number: +52 5523351588; Email: leukemiachop33@gmail.com
• Study Contact Backup: Name: Ernesto Villagran, MD; Phone Number: 52 7771358561; Email: nerev16@gmail.com

Study Locations

• Mexico
  • Mexico City
    • Mexico City, Mexico City, Mexico, 06720
      • Recruiting
      • Hospital General de México Dr. Eduardo Liceaga
      • Contact: Christian O Ramos, MD; Phone Number: 52 55 2789 2000; Email: enre16@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with a de novo diagnosis of acute lymphoblastic leukemia, considered frail according to the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale or with a Karnofsky Performance Score below 80%, indicating a high risk of severe chemotherapy-related toxicity, or patients who have received induction therapy and experienced severe and limiting toxicity.

Description

Inclusion Criteria:

• Diagnosed with acute lymphoblastic leukemia (ALL) according to the World Health Organization (WHO) criteria
• Older than 18 years old
• ECOG Performance Status Scale >1 or the Karnofsky Performance Status (KPS) <80%.
• Comorbidities: diabetes mellitus, arterial hypertension, thrombotic events, endocrine disorders, or any condition that hinders the administration of full-dose chemotherapy.
• Toxicity prior to a standard chemotherapy regimen.
• Both genders
• Over 18 years of age
• No upper age limit
• Signed informed consent

Exclusion Criteria:

´- Patients refractory to induction treatment

• Patients who have previously received a low-intensity regimen due to comorbidities
• Biphenotypic leukemia
• CNS involvement at diagnosis requiring radiotherapy
• Patients whose survival is expected to be less than 48 hours due to leukemiarelated complications
• Patients with a history of ischemic or hemorrhagic stroke or severe neurological deterioration
• Pregnant patients

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Frail ALL patients by ECOG >1 or KPS <80%, or with severe toxicity from induction therapy; Patients newly diagnosed with acute lymphoblastic leukemia (ALL) who are considered clinically frail based on an ECOG performance status score greater than 1 or a Karnofsky score below 80%, indicating a high risk of severe chemotherapy-related toxicity. This group also includes patients who have previously received induction therapy and experienced severe, limiting toxicity that prevents continuation of intensive treatment regimens. These criteria identify a vulnerable population for whom standard chemotherapy may not be suitable, necessitating alternative, less intensive treatment approaches to reduce toxicity while maintaining therapeutic efficacy

Drug: Patients meeting criteria will receive DA-EPOCH via central line for 5 days every 21 days, with monitoring, supportive care, transfusions, prophylaxis, and G-CSF for 5 doses per cycle; After patient selection and confirmation of inclusion criteria, the DA-EPOCH treatment regimen will be initiated. It is typically administered through a central line over 5 days, during which adverse events will be closely monitored. Each treatment cycle lasts 21 days. All patients will receive the same level of care as those undergoing high-intensity chemotherapy, including monitoring of transfusion needs, supportive care with prophylactic medications, and the administration of colony-stimulating factors, with a total of 5 doses per cycle. The treatment regimen consists of six cycles, during which intrathecal chemotherapy will be administered to prevent central nervous system relapse. This prophylaxis will be given between each cycle. After completing the six cycles, patients will continue with a maintenance regimen consisting of 6-mercaptopurine at 50 mg/m² of body surface area from Monday to Friday, along with weekly intramuscular methotrexate (50 mg), total duration for 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the proportion of overall survival and disease-free survival	For the survival analysis, the Kaplan-Meier method will be used, which is a non-parametric technique employed to estimate the survival function from time-to-event data.	From enrollment until 1 year after the end of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the proportion of complete remissions (<5% blasts per field) after the first 4 weeks of induction therapy and the proportion of measurable residual disease (proportion of cells) at 6 weeks.	Complete remission (CR) will be evaluated by bone marrow aspiration and optical microscopy review at 4 weeks after induction, while measurable residual disease (MRD) will be assessed also by bone marrow aspiration ans measured by flow cytometry at 6 weeks of treatment.	Complete Remision (CR) at 4 weeks after induction and measurable residual disease (MRD) at 6 weeks of treatment.
To establish the proportion of serious adverse events associated with the chemotherapy regimen.	These will be graded according to the adverse events scale. The National Comprehensive Cancer Network (NCCN) adverse events scale, known as the 'NCCN Common Terminology Criteria for Adverse Events' (NCCN CTCAE), is a tool used to classify the severity of adverse events that occur during clinical trials of cancer treatments.	From enrollment until 1 year after the end of treatment.
To describe the proportion of severe neutropenia events and treatment-related mortality	Neutropenia events associated with chemotherapy will be quantified in each cycle, and their proportion will be established per administered cycle	From enrollment until 1 year after the end of treatment.
To describe the length of hospital stay in days.	The days of hospital stay will be quantified for each cycle of chemotherapy.	From hospital admission to the last day of stay for each administered cycle (each cycle is 21 days).

Collaborators and Investigators

• Sponsor: Hospital General de Mexico
• Investigators: Principal Investigator: Christian O Ramos, MD, Hospital General de México Dr. Eduardo Liceaga

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2025
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): July 26, 2026

Study Registration Dates

• First Submitted: August 27, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: acute lymphoblastic leukemia; EPOCH
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Biological Factors; Carbohydrates; Patient Care; Health Services; Health Care Facilities Workforce and Services; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Biological Therapy; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Palliative Care; Granulocyte Colony-Stimulating Factor; Blood Transfusion
• Other Study ID Numbers: HGMexicoEduardoLiceaga

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes