Acute Lymphoblastic Leukemia, in RelapsePhase 2NCT06034561
Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia
A Phase 2 study testing Bortezomib in people with Acute Lymphoblastic Leukemia, in Relapse and Acute Lymphoblastic Leukemia With Failed Remission, run by Instituto do Cancer do Estado de São Paulo at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia With Failed Remission
- What is being tested?
- Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Apr 2024to Aug 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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;
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Instituto do Cancer do Estado de Sao Paulo
São Paulo, São Paulo, 01246000
Wellington F Silva, MD PhD, 551138944677, wellington.fernandes@hc.fm.usp.br
About this study
Official title: Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia in Adults
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.
Read the 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:
- To determine the safety and feasibility of a bortezomib-based regimen for salvage relapsed/refractory ALL in our setting.
- To determine the rate of patients who are able to proceed with HSCT after the treatment.
- To calculate event-free survival and overall survival after the salvage regimen for relapsed/refractory ALL.
- To calculate the rate of measurable residual disease (MRD) negative status after the treatment.
- 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
- Being tested
- Bortezomib
- Keywords
- Acute lymphoblastic leukemia, Bortezomib, Salvage therapy, Bridge therapy, Response rate
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Vincristine, Doxorubicin, Peg-asparaginase, Dexamethasone
Patients should receive one or two courses of this regimen, aiming to achieve complete remission as a bridge to proceed with allogeneic HSCT.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | 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. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response
Disappearance of lymphoid blasts in peripheral blood, with fewer than 5% of lymphoid blasts quantified in the bone marrow aspirate through immunophenotyping.
Measured: 30 days
Secondary outcomes (4)
Event-free survival
Time interval between study enrollment and the occurrence of an event (non-response, relapse, or death) or last follow-up (censorship).
Measured: 1 year
Overall survival
Time interval between study enrollment and the occurrence of death or last follow-up (censorship).
Measured: 1 year
Rate of MRD-negativity
Absence of pathological lymphoid blasts in a bone marrow sample detected through immunophenotyping with a minimum sensitivity of 10-4.
Measured: 60 days
Rate of allogeneic hematopoietic stem-cell transplantation
Proportion of patients who successfully underwent allogeneic hematopoietic stem-cell transplantation after the study therapy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start1 Apr 2024
- Primary completionAug 2028 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia, in RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto do Cancer do Estado de São Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Libbs Farmacêutica LTDA
- Responsible party
- Sponsor
- Investigators
- Wellington Silva, MD PhD, Principal investigator, Instituto do Cancer do Estado de Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06034561
- Sponsor's protocol ID
- 4009/23
- Status last verified
- Apr 2025
- First submitted
- 6 Sep 2023
- Last updated
- 16 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia in Adults
- ClinicalTrials.gov ID
- NCT06034561
- Acronym / sponsor ID
- 4009/23
- Conditions
- Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia With Failed Remission
- Keywords
- Acute lymphoblastic leukemia, Bortezomib, Salvage therapy, Bridge therapy, Response rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Instituto do Cancer do Estado de São PauloUniversity, hospital or other
- Collaborators
- Libbs Farmacêutica LTDA
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 13 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To determine the safety and feasibility of a bortezomib-based regimen for salvage relapsed/refractory ALL in our setting.
- To determine the rate of patients who are able to proceed with HSCT after the treatment.
- To calculate event-free survival and overall survival after the salvage regimen for relapsed/refractory ALL.
- To calculate the rate of measurable residual disease (MRD) negative status after the treatment.
- To examine the rate of febrile neutropenia, liver toxicity, neurotoxicity, and treatment-related mortality after this regimen in relapsed/refractory ALL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: BortezomibPatients 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. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (14 listed)
- Burkitt leukemia;
- Prior myeloproliferative disease;
- Drug allergies;
- Eastern Cooperative Oncology Group (ECOG) scale >2;
- Total bilirubin>2x upper limit of normal (ULN);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: Vincristine, Doxorubicin, Peg-asparaginase, DexamethasonePatients should receive one or two courses of this regimen, aiming to achieve complete remission as a bridge to proceed with allogeneic HSCT. | Drug | Bortezomib |
Primary outcome
Complete response
Time frame: 30 days
Disappearance of lymphoid blasts in peripheral blood, with fewer than 5% of lymphoid blasts quantified in the bone marrow aspirate through immunophenotyping.
4 secondary outcomes
Event-free survival
Time frame: 1 year
Overall survival
Time frame: 1 year
Rate of MRD-negativity
Time frame: 60 days
Rate of allogeneic hematopoietic stem-cell transplantation
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wellington Silva, MD PhD principal investigator
Instituto do Cancer do Estado de Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Acute Lymphoblastic Leukemia, in Relapse and Acute Lymphoblastic Leukemia With Failed Remission, run by Instituto do Cancer do Estado de São Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Graziela S Silva (551138934677, graziela.sasilva@hc.fm.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.