Clinical trial NCT05137860: Efficacy of the Use of Bortezomib for the Treatment of Relapsed Leukemia or Positive MRD
Official title: Efficacy of the Use of Bortezomib for the Treatment of Relapsed Leukemia or Positive Minimal Residual Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia, in Relapse
Chemotherapeutic Toxicity
Minimal Residual Disease
Keywords: Acute lymphoblastic leukemia
Bortezomib
Relapse
Minimal Residual Disease
Toxicity
Lead sponsor: Hospital General de Mexico
Sponsor class: OTHER_GOV
First posted: 2021-11-30
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Clinical Randomized Trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Survival Outcome
timeFrame: 3 months
measure: Hospital stay
timeFrame: 3 months
measure: Leukocytes count
timeFrame: 3 months
measure: Platelets count
timeFrame: 3 months
measure: Date of Remission
timeFrame: 3 month
Secondary outcomes:
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Hospital General de México "Dr. Eduardo Liceaga"
Study officials:
affiliation: Hospital General de Mexico
name: Adolfo Martinez Tovar, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.