Myeloid Leukemia, AcutePhase 2PTBCyNCT04943757
Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies
A Phase 2 study testing Bendamustine Hydrochloride and Cyclophosphamid in people with Myeloid Leukemia, Acute and Chronic Myeloid Leukemia, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
Trial summary
Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Myeloid Leukemia, Acute, Chronic Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Bendamustine Hydrochloride and Cyclophosphamid
- 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 May 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with indication for allogeneic hematopoietic stem cell transplantation
- Patients with 5-10/10 HLA-matched related or unrelated 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
- Diagnosis:
- Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms
- Salvage hematopoietic stem cell transplantation defined as:
- Acute myeloid leukemia: >5% of clonal blasts despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: >10% of blasts despite previous therapy with -7 or complex karyotype, or p53 mutation Chronic myeloid leukemia: blast crisis or acceleration phase despite at least 3 previous lines of TKIs Myeloprolipherative neoplasms : high tumor burden despite previous therapy, including >20 000 WBC/ ul or splenomegaly >15 cm
- No severe concurrent illness
Who cannot join
- 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
- Uncontrolled bacterial or fungal infection at the time of enrollment
Show all 10Show fewer
- 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
Official title: Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)
Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
- Conditions
- Myeloid Leukemia, Acute, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm
- Being tested
- Bendamustine Hydrochloride, Cyclophosphamid
- Keywords
- Bendamustine, Cyclophosphamide, Graft-versus-host disease, Graft-versus-leukemia effect, Refractory, Acute Myeloid leukemia, Hematopoietic Stem Cell Transplantation, Allogeneic
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Myeloproliferative Disorders, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bendamustine HydrochlorideDrug
50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation
CyclophosphamidDrug
25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| PTBCy graft-versus-host disease prophylaxis | Experimental | Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration Receives: Drug: Bendamustine Hydrochloride; Drug: Cyclophosphamid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival analysis [ Time Frame: 1 year ]
Measure: Kaplan-Meier estimate of death or relapse, or graft failure
Measured: 1 year
Secondary outcomes (7)
- Incidence of Cytokine release syndrome
Proportion of patients with cytokine release syndrome according to ASBMT Consensus Grading for Cytokine Release Syndrome, 2018
Measured: 100 days
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.
Measured: 100 days
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: 1 year
Relapse rate analysis
Cumulative incidence of patients with relapse
Measured: 1 year
Non-relapse mortality analysis
Cumulative incidence of patients with mortality without hematological relapse of malignancy
Measured: 1 year
Overall survival analysis
Kaplan-Meier estimate of death from all causes
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 posted29 Jun 2021
- Study start21 Jan 2021
- Primary completion30 May 2024
- Study completion30 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myeloid Leukemia, AcuteStudies 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
- NCT04943757
- Sponsor's protocol ID
- 05/21-n
- Acronym
- PTBCy
- Status last verified
- Oct 2024
- First submitted
- 21 Jun 2021
- Last updated
- 15 Oct 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.
Publications
Moiseev I, Bondarenko S, Morozova E, Vlasova Y, Dotsenko A, Epifanovskaya O, Babenko E, Botina A, Baykov V, Surkova E, Lapin S, Beynarovich A, Borzenkova E, Golosgchapov O, Kanunnikov M, Kudyasheva O, Ovechkina V, Pirogova O, Porunova V, Rudakova T, Smikova O, Smirnova A, Afansyev B. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study. Transplant Cell Ther. 2021 Jul;27(7):601.e1-601.e7. doi: 10.1016/j.jtct.2021.03.032. Epub 2021 May 7.
PubMed 33845259
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)
- ClinicalTrials.gov ID
- NCT04943757
- Acronym / sponsor ID
- PTBCy / 05/21-n
- Conditions
- Myeloid Leukemia, Acute, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm
- Keywords
- Bendamustine, Cyclophosphamide, Graft-versus-host disease, Graft-versus-leukemia effect, Refractory, Acute Myeloid leukemia, Hematopoietic Stem Cell Transplantation, Allogeneic
- 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 May 2024 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 29 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.
Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PTBCy graft-versus-host disease prophylaxis | Experimental | Drug: Bendamustine Hydrochloride, Drug: CyclophosphamidDays +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with indication for allogeneic hematopoietic stem cell transplantation
- Patients with 5-10/10 HLA-matched related or unrelated 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
- Diagnosis:
- Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms
Key exclusion criteria (10 listed)
- 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
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 Hydrochloride50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation | Drug | PTBCy graft-versus-host disease prophylaxis |
| Cyclophosphamid25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation | Drug | PTBCy graft-versus-host disease prophylaxis |
Primary outcome
Event-free survival analysis [ Time Frame: 1 year ]
Time frame: 1 year
Measure: Kaplan-Meier estimate of death or relapse, or graft failure
7 secondary outcomes
- Incidence of Cytokine release syndrome
Time frame: 100 days
Incidence of HSCT-associated adverse events (safety and toxicity)
Time frame: 100 days
Incidence of acute GVHD grade II-IV
Time frame: 125 days
Incidence of moderate and severe chronic GVHD
Time frame: 1 year
Relapse rate analysis
Time frame: 1 year
Non-relapse mortality analysis
Time frame: 1 year
Overall survival analysis
Time frame: 1 year
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 15 Oct 2024.
- Background: PubMed 33845259Moiseev I, Bondarenko S, Morozova E, Vlasova Y, Dotsenko A, Epifanovskaya O, Babenko E, Botina A, Baykov V, Surkova E, Lapin S, Beynarovich A, Borzenkova E, Golosgchapov O, Kanunnikov M, Kudyasheva O, Ovechkina V, Pirogova O, Porunova V, Rudakova T, Smikova O, Smirnova A, Afansyev B. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study. Transplant Cell Ther. 2021 Jul;27(7):601.e1-601.e7. doi: 10.1016/j.jtct.2021.03.032. Epub 2021 May 7.
- 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.
Related trials for Myeloid Leukemia, Acute
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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 Bendamustine Hydrochloride and Cyclophosphamid in people with Myeloid Leukemia, Acute and Chronic 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 8 inclusion and 10 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 15 Oct 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?
Event-free survival analysis [ Time Frame: 1 year ] (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04943757, which also lists 1 linked publication.
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 15 Oct 2024.