Leukemia, Acute LymphoblasticPhase 2FluBuBeNCT04942730
Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
A Phase 2 study testing Fludarabine, Bendamustine Hydrochloride and Busulfan in people with Leukemia, Acute Lymphoblastic and Myeloid Leukemia, Acute, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
Trial summary
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning 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 10-20% of graft failures. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Acute Lymphoblastic, Myeloid Leukemia, Acute, Biphenotypic Acute Leukemia
- What is being tested?
- Fludarabine, Bendamustine Hydrochloride and Busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteRussia
- Study dates
- 21 Jan 2021to 30 Apr 2024
- 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 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
- 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
- No second malignancies requiring treatment
- No severe concurrent illness
Who cannot join
- Titer of anti-HLA antibodies ≥ 5000 at the time of inclusion
- Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- Respiratory distress >grade I
- Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- Creatinine clearance < 60 mL/min
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- Uncontrolled bacterial or fungal infection at the time of enrollment
- Requirement for vasopressor support at the time of enrollment
- Karnofsky index <30%
- Pregnancy
- Somatic or psychiatric disorder making the patient unable to sign informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning 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 10-20% of graft failures. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of disease. Furthermore combination of fludarabine and bendamustine was sufficient to facilitate engraftment in patients with chronic lymphocytic leukemia and lymphomas. The aim of the study is to evaluate whether addition of bendamustine to fladarabine and busulfan conditioning reduces the risk of primary graft failure after haploidentical allograft.
- Conditions
- Leukemia, Acute Lymphoblastic, Myeloid Leukemia, Acute, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Neoplasm
- Being tested
- Fludarabine, Bendamustine Hydrochloride, Busulfan, Cyclophosphamide, Mycophenolate Mofetil
- Keywords
- Fludarabine, Bendamustine, Busulfan, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic, Antineoplastic Agents, Alkylating
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute, Myelodysplastic Syndromes, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT
Bendamustine HydrochlorideDrug
130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT
BusulfanDrug
1 mg/kg po qid x 3 days, Days -5 through -3
CyclophosphamideDrug
50 mg/kg iv x 2 days, Days +3 through +4
45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35
Tacrolimus 5Mg CapDrug
0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml.
| Study group | Role | What they receive |
|---|---|---|
| FluBuBe | Experimental | Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 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 +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration Receives: Drug: Fludarabine; Drug: Bendamustine Hydrochloride; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Tacrolimus 5Mg Cap |
What is being measured
The primary outcome is the main question the study is designed to answer.
- Incidence of primary and secondary graft failure
Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism
Measured: 100 days
Secondary outcomes (8)
- Incidence of HSCT-associated adverse events (safety and toxicity)
Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al. criteria. 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: [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Incidence of acute GVHD grade II-IV
Cumulative incidence of patients with acute GVHD II-IV grade
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.
Measured: 365 days
- Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Measured: 2 years
- Overall survival analysis
Kaplan-Meier estimate of death from all causes
Measured: 2 years
- Event-free survival analysis
Kaplan-Meier estimate of death or relapse
Measured: 2 years
- Relapse rate analysis
Cumulative incidence of patients with relapse
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 posted28 Jun 2021
- Study start21 Jan 2021
- Primary completion30 Apr 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Acute LymphoblasticStudies 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 (actual)
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
- NCT04942730
- Sponsor's protocol ID
- 06/21-n
- Acronym
- FluBuBe
- Status last verified
- May 2024
- First submitted
- 21 Jun 2021
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Request for sharing data with the study plan for the data will be evaluated under common conditions by Pavlov University Ethical Committee.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)
- ClinicalTrials.gov ID
- NCT04942730
- Acronym / sponsor ID
- FluBuBe / 06/21-n
- Conditions
- Leukemia, Acute Lymphoblastic, Myeloid Leukemia, Acute, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Neoplasm
- Keywords
- Fludarabine, Bendamustine, Busulfan, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic, Antineoplastic Agents, Alkylating
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
- Study start
- 21 Jan 2021 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 28 Jun 2021 (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 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 10-20% of graft failures. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of disease. Furthermore combination of fludarabine and bendamustine was sufficient to facilitate engraftment in patients with chronic lymphocytic leukemia and lymphomas. The aim of the study is to evaluate whether addition of bendamustine to fladarabine and busulfan conditioning reduces the risk of primary graft failure after haploidentical allograft.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FluBuBe | Experimental | Drug: Fludarabine, Drug: Bendamustine Hydrochloride, Drug: Busulfan, Drug: Cyclophosphamide, Drug: Mycophenolate Mofetil, Drug: Tacrolimus 5Mg CapDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 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 +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
- 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
- No second malignancies requiring treatment
- No severe concurrent illness
Key exclusion criteria (11 listed)
- Titer of anti-HLA antibodies ≥ 5000 at the time of inclusion
- Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- Respiratory distress >grade I
- 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 |
|---|---|---|
| Fludarabine30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT | Drug | FluBuBe |
| Bendamustine Hydrochloride130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT | Drug | FluBuBe |
| Busulfan1 mg/kg po qid x 3 days, Days -5 through -3 | Drug | FluBuBe |
| Cyclophosphamide50 mg/kg iv x 2 days, Days +3 through +4 | Drug | FluBuBe |
| Mycophenolate Mofetil45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35 | Drug | FluBuBe |
| Tacrolimus 5Mg Cap0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml. | Drug | FluBuBe |
Primary outcome
- Incidence of primary and secondary graft failure
Time frame: 100 days
Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism
8 secondary outcomes
- 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: [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
- Incidence of acute GVHD grade II-IV
Time frame: 125 days
- Incidence of moderate and severe chronic GVHD
Time frame: 365 days
- Non-relapse mortality analysis
Time frame: 2 years
- Overall survival analysis
Time frame: 2 years
- Event-free survival analysis
Time frame: 2 years
- Relapse rate analysis
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Individual participant dataSharing planned: Yes. Request for sharing data with the study plan for the data will be evaluated under common conditions by Pavlov University Ethical Committee.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Fludarabine, Bendamustine Hydrochloride and Busulfan in people with Leukemia, Acute Lymphoblastic and Myeloid Leukemia, Acute, 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 5 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: finished, as of the sponsor's last update on 7 May 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- Incidence of primary and secondary graft failure (time frame: 100 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 7 May 2024.