Cytarabine+Thiotepa + Fludarabine + BusulfanPhase 2NCT05598593
Modified TBF Regimen as Conditioning Regimen Prior to Allo-HSCT for T-ALL/LBL
A Phase 2 study testing cytarabine+thiotepa+ fludarabine + busulfan in people with Cytarabine+Thiotepa + Fludarabine + Busulfan and T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of T-lineage precursor cells. Read more about this study
- Who is it for?
- Ages 4 to 65 years
- Conditions the study is for
- Cytarabine+Thiotepa + Fludarabine + Busulfan, T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma
- What is being tested?
- cytarabine+thiotepa+ fludarabine + busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 23 Oct 2022to Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 4 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age younger than 65 years
- Patients diagnosed with T cell acute lymphoblastic leukemia/lymphoma , T-ALL/LBL according to WHO diagnostic criteria.
- Patients who have donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
- ECOG body status score 0-2.
- Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/ L; PLT >=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%).
- Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.
Who cannot join
- Patients who with severe cardiac insufficiency, cardiac ejection fraction EF is less than 60%; or severe arrhythmia, the investigator can not tolerate conditioning chemotherapy;
- In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate conditioning chemotherapy;
- Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of conditioning chemotherapy;
- In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate conditioning chemotherapy;
- In patients with severe active infection, the researchers evaluated that they could not tolerate conditioning chemotherapy;
- Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
- Other reasons why the researchers could not be selected.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou
Yi Luo, MD, 86-13666609126, luoyijr@zju.edu.com
Lizhen Liu, MD, 86-15858222740, lizhenliuzju@126.com
About this study
Official title: Modified TBF Regimen as Conditioning Regimen Prior to Allogeneic Hematopoietic Cell Transplantation for T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma：Phase II Study
T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of T-lineage precursor cells. The long-term cure rate of pediatric patients with T-ALL/LBL reaches 90%, but long-term survival of adult patients is less than 60%. Moreover, patients with high-risk factors such as PTEN/NRAS gene mutation, early T cell precursor (ETP) phenotype or positive minimal residual disease (MRD) have high rates of chemoresistance and dismal outcome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can significantly improve the prognosis of high-risk T-ALL/LBL. Total body irradiation (TBI)-based conditioning chemotherapy regimen is the preferred regimen for allo-HSCT in children and young adults with ALL because of lower relapse rates and satisfactory survival. Different from children, the non-relapse-related mortality (NRM) after TBI-based preconditioning in adults (especially those >35 years old) was reported as high as 38%. In addition, serious sequelae after TBI seriously affect the quality of life and non-radiation conditioning chemotherapy regimens are urgently needed for T-ALL/LBL. The reported recurrence rates after BUCY (busulfan + cyclophosphamide) conditioning regimen for T-ALL as 41.2%. -56.7% and long-term survival was only 30-50%. Thiotepa is an ethyleneimine alkylating agent with anti-tumor effects and immunosuppressive effects, thus is widely used in conditioning regimen before HSCT. Retrospective paired analysis from EBMT indicated conditioning regimen thiotepa achieved similar relapse rates, long-term survival and faster granulocyte and platelet engraftment than TBI regimen. A recent retrospective study of childhood ALL from Turkey also reported that the TBF(thiotepa + fludarabine + busulfan) regimen had a recurrence rate of only 11.9% , a non-relapse mortality rate of 14.0% and a long-term survival of 79.1%. Data from a large retrospective paired study suggested TBF regimen can significantly reduce the relapse rate of acute myeloid leukemia after the first remission (HR=0.4, CI 0.2-0.7, P = .02) without increasing treatment related deaths compared with the traditional BUCY regimen. Based on these data, we modified the TBF regimen with additional cytarabine for allo-HSCT in T-ALL/LBL with expection to reduced disease relapse and improved long-term survival.
- Conditions
- Cytarabine+Thiotepa + Fludarabine + Busulfan, T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma
- Being tested
- cytarabine+thiotepa+ fludarabine + busulfan
- Keywords
- allogeneic hematopoietic stem cell transplantation, T cell Acute Lymphoblastic Leukemia/Lymphoblastic lymphoma, thiotepa
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytarabine+thiotepa+ fludarabine + busulfanDrug
cytarabine+thiotepa+ fludarabine + busulfan intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| Modified TBF Conditioning Regimen | Experimental | thiotepa 5mg/kg/d d-9 to d-8, cytarabine 0-4.0 g/m2/d d-7 to d-6(adjusted according to patients' age and HCT-CI index), fludarabine 30mg/m2/d d-7 to d-3, busulfan 3.2mg/m2/d d-5 to d-3 Receives: Drug: cytarabine+thiotepa+ fludarabine + busulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival
2-year DFS
Measured: 2 year
Secondary outcomes (4)
incidence of toxic reaction
2-year incidence of toxic reaction
Measured: 2 year
overall survival
2-year OS
Measured: 2 year
umulative incidence of relapse
2-year incidence of relapse
Measured: 2 year
ncidence of acute and or chronic graft verus host disease
2-year incidence of cGVHD
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start23 Oct 2022
- Primary completionSep 2024 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytarabine+Thiotepa + Fludarabine + BusulfanStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang UniversityThe sponsor's other registered studies.
- 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
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yi Luo, M.D., Principal investigator, First Affilaated Hospital of Medical School of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05598593
- Sponsor's protocol ID
- ZJU-HSCT-MTBF
- Status last verified
- Oct 2022
- First submitted
- 26 Oct 2022
- Last updated
- 28 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modified TBF Regimen as Conditioning Regimen Prior to Allogeneic Hematopoietic Cell Transplantation for T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma：Phase II Study
- ClinicalTrials.gov ID
- NCT05598593
- Acronym / sponsor ID
- ZJU-HSCT-MTBF
- Conditions
- Cytarabine+Thiotepa + Fludarabine + Busulfan, T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma
- Keywords
- allogeneic hematopoietic stem cell transplantation, T cell Acute Lymphoblastic Leukemia/Lymphoblastic lymphoma, thiotepa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 23 Oct 2022 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 28 Oct 2022 (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.
T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of T-lineage precursor cells. The long-term cure rate of pediatric patients with T-ALL/LBL reaches 90%, but long-term survival of adult patients is less than 60%. Moreover, patients with high-risk factors such as PTEN/NRAS gene mutation, early T cell precursor (ETP) phenotype or positive minimal residual disease (MRD) have high rates of chemoresistance and dismal outcome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can significantly improve the prognosis of high-risk T-ALL/LBL. Total body irradiation (TBI)-based conditioning chemotherapy regimen is the preferred regimen for allo-HSCT in children and young adults with ALL because of lower relapse rates and satisfactory survival. Different from children, the non-relapse-related mortality (NRM) after TBI-based preconditioning in adults (especially those >35 years old) was reported as high as 38%. In addition, serious sequelae after TBI seriously affect the quality of life and non-radiation conditioning chemotherapy regimens are urgently needed for T-ALL/LBL. The reported recurrence rates after BUCY (busulfan + cyclophosphamide) conditioning regimen for T-ALL as 41.2%. -56.7% and long-term survival was only 30-50%. Thiotepa is an ethyleneimine alkylating agent with anti-tumor effects and immunosuppressive effects, thus is widely used in conditioning regimen before HSCT. Retrospective paired analysis from EBMT indicated conditioning regimen thiotepa achieved similar relapse rates, long-term survival and faster granulocyte and platelet engraftment than TBI regimen. A recent retrospective study of childhood ALL from Turkey also reported that the TBF(thiotepa + fludarabine + busulfan) regimen had a recurrence rate of only 11.9% , a non-relapse mortality rate of 14.0% and a long-term survival of 79.1%. Data from a large retrospective paired study suggested TBF regimen can significantly reduce the relapse rate of acute myeloid leukemia after the first remission (HR=0.4, CI 0.2-0.7, P = .02) without increasing treatment related deaths compared with the traditional BUCY regimen. Based on these data, we modified the TBF regimen with additional cytarabine for allo-HSCT in T-ALL/LBL with expection to reduced disease relapse and improved long-term survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Modified TBF Conditioning Regimen | Experimental | Drug: cytarabine+thiotepa+ fludarabine + busulfanthiotepa 5mg/kg/d d-9 to d-8, cytarabine 0-4.0 g/m2/d d-7 to d-6(adjusted according to patients' age and HCT-CI index), fludarabine 30mg/m2/d d-7 to d-3, busulfan 3.2mg/m2/d d-5 to d-3 |
Who may qualify
- Ages
- 4 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age younger than 65 years
- Patients diagnosed with T cell acute lymphoblastic leukemia/lymphoma , T-ALL/LBL according to WHO diagnostic criteria.
- Patients who have donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
- ECOG body status score 0-2.
- Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/ L; PLT >=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%).
Key exclusion criteria (7 listed)
- Patients who with severe cardiac insufficiency, cardiac ejection fraction EF is less than 60%; or severe arrhythmia, the investigator can not tolerate conditioning chemotherapy;
- In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate conditioning chemotherapy;
- Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of conditioning chemotherapy;
- In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate conditioning chemotherapy;
- In patients with severe active infection, the researchers evaluated that they could not tolerate conditioning chemotherapy;
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 |
|---|---|---|
| cytarabine+thiotepa+ fludarabine + busulfancytarabine+thiotepa+ fludarabine + busulfan intravenous injection | Drug | Modified TBF Conditioning Regimen |
Primary outcome
Disease free survival
Time frame: 2 year
2-year DFS
4 secondary outcomes
incidence of toxic reaction
Time frame: 2 year
overall survival
Time frame: 2 year
umulative incidence of relapse
Time frame: 2 year
ncidence of acute and or chronic graft verus host disease
Time frame: 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Individual participant dataSharing planned: No
Related trials for Cytarabine+Thiotepa + Fludarabine + Busulfan
Not yet recruitingPhase 2
The Safety and Efficacy of the Regimen of Thiotepa + Fludarabine +Granulocyte Colony-Stimulating Factor+ Cytarabine + Busulfan in Single Unrelated Umbilical Cord Blood Transplantation
Hematologic Malignancies
RecruitingObservational study
Intensive Conditioning withTHI/Bu/Flu/Ara-C in Allo-HSCT for Myeloid Malignancies With Extramedullary Involvement
Acute Myeloid Leukemia, Myelodysplastic Neoplasm
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. This study is not recruiting at the moment.
Yi Luo, M.D. principal investigator
First Affilaated Hospital of Medical School of Zhejiang University
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 cytarabine+thiotepa+ fludarabine + busulfan in people with Cytarabine+Thiotepa + Fludarabine + Busulfan and T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
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 6 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 28 Oct 2022. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yi Luo, M.D. (+86057187233801, luoyijr@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 2 year). 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 28 Oct 2022.