Efficacy of the Use of Bortezomib for the Treatment of Relapsed Leukemia or Positive MRD

Efficacy of the Use of Bortezomib for the Treatment of Relapsed Leukemia or Positive Minimal Residual Disease

Various drugs have been added to different treatment regimens in order to improve the response rate in patients with Acute Lymphoblastic Leukemia, however, it has been shown that adding Bortezomib to the relapsing regimen improves the proportion of second complete remissions without increasing chemotherapy toxicity. Therefore, proteasome inhibitors can drastically modify the prognosis of patients, since their synergy with drugs such as steroids has positioned them as an attractive strategy.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Chemotherapeutic Toxicity; Minimal Residual Disease
• Intervention / Treatment: Drug: Bortezomib

Detailed Description

Mortality associated with leukemia has decreased due to the use of various chemotherapy combinations, the addition of new agents, or the chemical modification of existing drugs. Despite advances in treatment, the prognosis in the adult population continues to be unfavorable. About 25% of the patients will be refractory to the first treatment regimen and the rest will have a disease-free survival below 40%. The chemotherapy intensity reduction strategy based on risk stratification according to Minimal Residual Disease (MRD) is a strategy used by various pediatric centers in order to detect patients at high risk of relapse.

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 06720
    • Recruiting
    • Hospital General de México "Dr. Eduardo Liceaga"
    • Contact: Christian O Ramos Peñafiel, PhD; Phone Number: 2020 +52 55 2789 2000; Email: leukemiachop@hotmail.com
    • Sub-Investigator: Carlos Martínez Murillo, PhD
    • Sub-Investigator: Humberto Castellanos Sinco, PhD
    • Sub-Investigator: Odín de la Mora Estrada, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a confirmatory diagnosis of Acute Lymphoblastic Leukemia relapsed to bone marrow described with more than 5% blasts in bone marrow at any stage of treatment or positivity of minimal residual disease at any stage of treatment.
• Patients who have signed their informed consent from the institution for hospitalization, and accepted the performance of the bone marrow study, and the administration of chemotherapy.

Exclusion Criteria:

• Patients with a diagnosis of phenotypic leukemia or bilinear leukemia
• Patients treated only with palliative regimen or transfusion support
• Patients without the administration of prophylaxis to the central nervous system by intrathecal chemotherapy
• Patients with lymphoblastic leukemia with a positive Philadelphia chromosome
• Patients with severe comorbidities may put treatment therapy at risk.
• Patient with a history of cardiac toxicity or arrhythmias associated with treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard Care Group; Each patient will receive their standard chemotherapy treatment for patients with relapsed Acute Lymphoblastic Leukemia based on the HyperCVAD scheme for a period of 12 weeks. Each chemotherapy cycle will be monitored by the health team corresponding to the Hematology service and the principal investigator.
EXPERIMENTAL: Bortezomib Treatment Group; Each patient will receive their standard chemotherapy treatment for patients with relapsed Acute Lymphoblastic Leukemia based on the HyperCVAD scheme in combination with Bortezomib for a period of 12 weeks. Each chemotherapy cycle will be monitored by the health team corresponding to the Hematology service and the principal investigator.	Drug: Bortezomib; Combination of Bortezomib with Standard Chemotherapy scheme for acute lymphoblastic patients in relapse.; Other Names: Intervention Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Outcome	The event in which patient is discharge from Hospital stay.	3 months
Hospital stay	Time in which patients stay in the Hospital before discharge	3 months
Leukocytes count	Number of leukocytes found in peripheral blood at the end of each chemotherapy cycle	3 months
Platelets count	Number of platelets found in peripheral blood at the end of each chemotherapy cycle	3 months
Date of Remission	Time in which the patient completes remission	3 month

Collaborators and Investigators

• Sponsor: Hospital General de Mexico

Publications and helpful links

General Publications

• Horton TM, Whitlock JA, Lu X, O'Brien MM, Borowitz MJ, Devidas M, Raetz EA, Brown PA, Carroll WL, Hunger SP. Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group. Br J Haematol. 2019 Jul;186(2):274-285. doi: 10.1111/bjh.15919. Epub 2019 Apr 7.
• Burton JD, Bamford RN, Peters C, Grant AJ, Kurys G, Goldman CK, Brennan J, Roessler E, Waldmann TA. A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4935-9. doi: 10.1073/pnas.91.11.4935.
• Bertaina A, Vinti L, Strocchio L, Gaspari S, Caruso R, Algeri M, Coletti V, Gurnari C, Romano M, Cefalo MG, Girardi K, Trevisan V, Bertaina V, Merli P, Locatelli F. The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood. Br J Haematol. 2017 Feb;176(4):629-636. doi: 10.1111/bjh.14505. Epub 2017 Jan 24.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 12, 2021
• Primary Completion (ANTICIPATED): December 22, 2022
• Study Completion (ANTICIPATED): June 23, 2023

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (ACTUAL): November 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 2, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Toxicity; Bortezomib; Relapse; Acute lymphoblastic leukemia; Minimal Residual Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Neoplastic Processes; Leukemia; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasm, Residual; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: HGMDI/21/204/03/67

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All participants and their information will be managed by intern investigators and will be kept secure for personal data protection according to Mexican laws.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No