Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia
50 patients around the world
Available in Brazil
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.
Instituto do Cancer do Estado de São Paulo
1Research sites
50Patients around the world
This study is for people with
Leukemia
Acute lymphoblastic leukemia
Requirements for the patient
To 60 Years
All Gender
Medical requirements
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).
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.
Sites
Fundação Faculdade de Medicina - Instituto do Cancer do Estado de São Paulo
Recruiting
Av. Dr. Arnaldo, 455 - Cerqueira César, Pacaembu - SP, 01246-903