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

NCT ID: NCT05137860

Last Updated: 2022-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-12
• Study Completion Date: 2023-06-23

Brief Summary

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.

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.

Conditions

Minimal Residual Disease; Acute Lymphoblastic Leukemia, in Relapse; Chemotherapeutic Toxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Combination of Bortezomib with Standard Chemotherapy scheme for acute lymphoblastic patients in relapse.

Interventions

Bortezomib

Combination of Bortezomib with Standard Chemotherapy scheme for acute lymphoblastic patients in relapse.

Intervention Type: DRUG

Other Intervention Names

Intervention Group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital General de Mexico

OTHER_GOV

Sponsor Role: lead

Responsible Party

Christian Omar Ramos-Peñafiel, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adolfo Martinez Tovar, PhD

Role: STUDY_DIRECTOR

Hospital General de Mexico

Locations

Hospital General de México "Dr. Eduardo Liceaga"

Mexico City, , Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

Christian O Ramos Peñafiel, PhD

Role: CONTACT

leukemiachop@hotmail.com

+52 55 27892000 ext. 2020

Adan G Gallardo Rodriguez, MSc

Role: CONTACT

nutriologo.agallardo8@gmail.com

+52 55 27892000 ext. 2020

Facility Contacts

Christian O Ramos Peñafiel, PhD

Role: primary

leukemiachop@hotmail.com

+52 55 2789 2000 ext. 2020

Adan G Gallardo-Rodriguez, MSc

Role: backup

nutriologo.agallardo8@gmail.com

+52 55 2789 2000 ext. 2020

References

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.

Reference Type: BACKGROUND

PMID: 8197160 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28116786 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30957229 (View on PubMed)

Other Identifiers

HGMDI/21/204/03/67

Identifier Type: -

Identifier Source: org_study_id