Acute Lymphoblastic LeukemiaPhase 2NCT06477549
BeFluBu vs FluBuRux Conditioning in Haploidentical HCT
A Phase 2 study testing Bendamustine Hydrochloride and Ruxolitinib in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
Trial summary
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Biphenotypic Acute Leukemia
- What is being tested?
- Bendamustine Hydrochloride and Ruxolitinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteRussia
- Study dates
- 21 Jun 2024to Jun 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
- Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, mixed lineage acute leukemia, lymphoblastic lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, myeloprolipherative neoplasm
- Age ≥18
- Malignant disease in hematologic response: <5% of clonal blasts in the bone marrow and no clonal blasts in peripheral blood.
- Patients with 5-9/10 HLA-matched related donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Peripheral blood stem cells or bone marrow as a graft source
Who cannot join
- Titer of anti-donor anti-HLA antibodies ≥ 5000 at the time of inclusion
- Moderate or severe cardiac disease: ejection fraction <50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
- Stroke within 3 months of inclusion, unless related to the underlying malignancy
- Severe decrease in pulmonary function: FEV1 <50% or DLCO<50% of predicted or respiratory distress or need for oxygen support;
- Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- Creatinine clearance < 40 mL/min
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- Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP> 70 mg/L
- Requirement for vasopressor support at the time of enrollment
- Karnofsky index <70%
- Pregnancy
- Somatic or psychiatric disorder making the patient unable to sign informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Yulia Vlasova contact
Russia1 site, 1 recruiting
- Recruiting
RM Gorbacheva Research Institute
Saint Petersburg, 197022
Ivan Moiseev, +79217961951, moisiv@mail.ru
Alexandr Kulagin, +78123386265, bmt-director@1spbgmu.ru
About this study
Official title: Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 7-20% of graft failures in different diseases. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of diseases. In two previously completed trials of addition of either bendamustine and ruxolitinib to conditioning we observed low rates of primary graft failure with both approaches. The study is the direct randomized comparisons of these two approaches with the primary aim of reducing composite events of primary graft failure, relapse and non-relapse mortality. The stratas for the study are Disease Risk Index (DRI) and the age of the haploidentical donor (<35 vs ≥35).
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Myeloproliferative Neoplasm, Myelodysplastic Syndromes
- Being tested
- Bendamustine Hydrochloride, Ruxolitinib
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute, Myeloproliferative Disorders, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bendamustine HydrochlorideDrug
Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days
RuxolitinibDrug
Days -7 through -2: ruxolitinib 5 mg tid per os
| Study group | Role | What they receive |
|---|---|---|
| FluBeBu conditioning | Experimental | Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days;Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os. Receives: Drug: Bendamustine Hydrochloride |
| FluBeRux conditioning | Active comparator | Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -2: ruxolitinib 5 mg tid per os; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
Measured: 2 years
Secondary outcomes (9)
Cumulative incidence of primary and secondary graft failure
Cumulative primary and secondary graft failure, competing risk is death and relapse
Measured: 365 days
Incidence of HSCT-associated adverse events (safety and toxicity)
Toxicity assessment is based on presence of NCI CTC AE 5.0 event grades 3-5. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2020. Transplant-associated microangiopathy incidence assessment is based on Harmonization criteria by Schoettler et al. All toxicity measurements will be aggregated as severity scores
Measured: 125 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease
Measured: 100 days
Cumulative incidence of acute GVHD grade II-IV
Cumulative incidence of patients with acute GVHD II-IV grade, competing risk is death, relapse and primary graft failure
Measured: 125 days
Incidence of moderate and severe chronic GVHD
Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria, competing risk is death, relapse and primary graft failure
Measured: 2 years
Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Measured: 2 years
Overall survival analysis
Measure: Kaplan-Meier estimate of death from all causes
Measured: 2 years
GVHD-relapse-free survival analysis
Measure: Kaplan-Meier estimate of death, acute GVHD grade III-IV, severe chronic GVHD or relapse
Measured: 2 years
Relapse cumulative incidence analysis
Cumulative incidence of patients with relapse, competing risk is non-relapse mortality
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2024
- Study start21 Jun 2024
- Primary completionJun 2028 (estimated)
- Study completionJun 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 LeukemiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Petersburg State Pavlov Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivan S Moiseev, St. Petersburg State Pavlov Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06477549
- Sponsor's protocol ID
- 14/24-n
- Status last verified
- Jun 2024
- First submitted
- 21 Jun 2024
- Last updated
- 27 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Written proposal to the department of scientific affairs of Pavlov University with a subsequent signed contract for research
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT06477549
- Acronym / sponsor ID
- 14/24-n
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Myeloproliferative Neoplasm, Myelodysplastic Syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
- Study start
- 21 Jun 2024 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 27 Jun 2024 (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.
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 7-20% of graft failures in different diseases. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of diseases. In two previously completed trials of addition of either bendamustine and ruxolitinib to conditioning we observed low rates of primary graft failure with both approaches. The study is the direct randomized comparisons of these two approaches with the primary aim of reducing composite events of primary graft failure, relapse and non-relapse mortality. The stratas for the study are Disease Risk Index (DRI) and the age of the haploidentical donor (<35 vs ≥35).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FluBeBu conditioning | Experimental | Drug: Bendamustine HydrochlorideDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days;Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os. |
| FluBeRux conditioning | Active comparator | Drug: RuxolitinibDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -2: ruxolitinib 5 mg tid per os; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +20: ruxolitinib 5 mg tid per os; Days +21 through 150: ruxolitinib 5 mg bid per os. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
- Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, mixed lineage acute leukemia, lymphoblastic lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, myeloprolipherative neoplasm
- Age ≥18
- Malignant disease in hematologic response: <5% of clonal blasts in the bone marrow and no clonal blasts in peripheral blood.
- Patients with 5-9/10 HLA-matched related donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
Key exclusion criteria (11 listed)
- Titer of anti-donor anti-HLA antibodies ≥ 5000 at the time of inclusion
- Moderate or severe cardiac disease: ejection fraction <50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
- Stroke within 3 months of inclusion, unless related to the underlying malignancy
- Severe decrease in pulmonary function: FEV1 <50% or DLCO<50% of predicted or respiratory distress or need for oxygen support;
- Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
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 |
|---|---|---|
| Bendamustine HydrochlorideDays -7 through -6: Bendamustine 90 mg/m2 iv x 2 days | Drug | FluBeBu conditioning |
| RuxolitinibDays -7 through -2: ruxolitinib 5 mg tid per os | Drug | FluBeRux conditioning |
Primary outcome
Event-free survival
Time frame: 2 years
Measure: Kaplan-Meier estimate of either relapse, primary or secondary graft failure or death from all causes
9 secondary outcomes
Cumulative incidence of primary and secondary graft failure
Time frame: 365 days
Incidence of HSCT-associated adverse events (safety and toxicity)
Time frame: 125 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Time frame: 100 days
Cumulative incidence of acute GVHD grade II-IV
Time frame: 125 days
Incidence of moderate and severe chronic GVHD
Time frame: 2 years
Non-relapse mortality analysis
Time frame: 2 years
Overall survival analysis
Time frame: 2 years
GVHD-relapse-free survival analysis
Time frame: 2 years
Relapse cumulative incidence analysis
Time frame: 2 years
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 27 Jun 2024.
- Individual participant dataSharing planned: Yes. Written proposal to the department of scientific affairs of Pavlov University with a subsequent signed contract for research
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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.
Yulia Vlasova contact
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 Bendamustine Hydrochloride and Ruxolitinib in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
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 11 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 27 Jun 2024. 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 Russia. 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 IVAN SERGEEVICH MOISEEV (0079217961951, moisiv@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (time frame: 2 years). 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 27 Jun 2024.