Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia

NCT ID: NCT06034561

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2029-08-31

Brief Summary

This is a interventional phase II study aiming to examine the complete response rate of a bortezomib-based salvage regimen in adults with refractory or relapsed acute lymphoblastic leukemia (ALL), seeking to compare outcomes with the available literature and with our historical data on relapsed/refractory ALL.

Detailed Description

Acute lymphoblastic leukemia (ALL) is a rare neoplasm in adults, with long-term survival rates approaching 50% with current regimens. Although high rates of complete response are achieved with the first-line therapy, many patients are primary refractory or may further relapse. Arguably, these patients have a more resistant disease with higher risk genetic alterations and a much less likely to be cured, which almost always only can be obtained by a following allogeneic hematopoietic stem-cell transplantation (HSCT). Therefore, strategies to salvage patients with detectable disease after induction blocks or with relapsed disease are crucial to prolong survival and potentially cure those patients, working as a bridge therapy to HSCT. Historically, patients with relapsed/refractory ALL have received multidrug regimens based on high-dose cytarabine, such as fludarabine, cytarabine and idarubicin (FLAG-IDA). Those regimens provide a 30-40% complete response rate with non-negligible toxicity. Recently, new targeted agents such as blinatumomab, inotuzumab, and cellular therapies have arisen for B-lineage disease, even though these agents are not available in the public health setting. Previous studies have tested salvage regimens for ALL encompassing proteasome inhibitors plus highly synergistic drugs (dexamethasone, vincristine, asparaginase, doxorubicin), with exciting outcomes in limited case series. For adults, these regimens are less studied. However, preliminary data suggest that they are less toxic and more potent since patients can receive different drug combinations that they had not been exposed to before. The primary objective of this study is to examine the complete response rate of this regimen in our population, aiming to compare with the available literature and with our historical data on relapsed/refractory ALL. Secondary objectives are:

1. To determine the safety and feasibility of a bortezomib-based regimen for salvage relapsed/refractory ALL in our setting.

2. To determine the rate of patients who are able to proceed with HSCT after the treatment.

3. To calculate event-free survival and overall survival after the salvage regimen for relapsed/refractory ALL.

4. To calculate the rate of measurable residual disease (MRD) negative status after the treatment.

5. To examine the rate of febrile neutropenia, liver toxicity, neurotoxicity, and treatment-related mortality after this regimen in relapsed/refractory ALL.

Conditions

Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphoblastic Leukemia With Failed Remission

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib

Patients with refractory or relapsed acute lymphoblastic leukemia will receive one-two courses of salvage regimen composed by:

• Bortezomib 1.3 mg/m2 I.V. D1,D4,D8,D11;
• Vincristine 1.5 mg/m2 I.V. (maximum at 2 mg) - D1, D8,D15,D22;
• Doxorubicin 60 mg/m2 I.V. - D1;
• Peg-asparaginase 2000 IU/m2 I.V. - D4 and D18;
• Dexamethasone 20 mg/m2 P.O. or I.V. (divided BID) - D1-D5 and D15-D19
• Intrathecal chemotherapy: methotrexate 12 mg + dexamethasone 2 mg.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Patients should receive one or two courses of this regimen, aiming to achieve complete remission as a bridge to proceed with allogeneic HSCT.

Interventions

Bortezomib

Patients should receive one or two courses of this regimen, aiming to achieve complete remission as a bridge to proceed with allogeneic HSCT.

Intervention Type: DRUG

Other Intervention Names

Vincristine; Doxorubicin; Peg-asparaginase; Dexamethasone; Methotrexate

Eligibility Criteria

Inclusion Criteria

• Patients between 16 and 60 years-old with refractory or relapsed ALL (≥1% of anomalous blasts by flow cytometry in bone marrow or peripheral blood) after one or two lines of therapy, regardless of their phenotype or baseline genetic alteration;
• Patients are eligible after allogeneic HSCT as long as patients are not actively being treated for graft-versus-host-disease (GvHD).

Exclusion Criteria

• Burkitt leukemia;
• Prior myeloproliferative disease;
• Drug allergies;
• Eastern Cooperative Oncology Group (ECOG) scale >2;
• Total bilirubin>2x upper limit of normal (ULN);
• Transaminases>5x ULN;
• Creatinine>2,5 mg/dl;
• Active uncontrolled infection;
• History of asparaginase-induced pancreatitis;
• Prior exposure to bortezomib;
• Heart failure New York Heart Association (NYHA) Class III or IV;
• Patients with more than 400mg/m2 lifetime exposure of anthracycline;
• Severe psychiatric disorder which prevents adequate compliance;
• Refusal to participate in the study.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Libbs Farmacêutica LTDA

INDUSTRY

Sponsor Role: collaborator

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wellington Silva, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Cancer do Estado de Sao Paulo

Locations

Instituto do Cancer do Estado de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Graziela S Silva

Role: CONTACT

graziela.sasilva@hc.fm.usp.br

551138934677

Bruna Moraes, MSc

Role: CONTACT

pesquisa.hematologia@hc.fm.usp.br

551126628112

Facility Contacts

Wellington F Silva, MD PhD

Role: primary

wellington.fernandes@hc.fm.usp.br

551138944677

Other Identifiers

4009/23

Identifier Type: -

Identifier Source: org_study_id