Leukemia, Chronic MyeloidPhase 2NCT02627573
Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT
A Phase 2 study testing Unrelated allogeneic stem cell transplantation, Busulfan and Fludarabine monophosphate in people with Leukemia, Chronic Myeloid and Myelodysplastic Syndromes, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
Trial summary
Purpose There is a growing evidence of high efficacy of post-transplantation cyclophocphomide (PTCy)-based GVHD prophylaxis in haploidentical and matched related and unrelated bone marrow transplantation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Chronic Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- What is being tested?
- Unrelated allogeneic stem cell transplantation, Busulfan and Fludarabine monophosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteRussia
- Study dates
- Jul 2015to 3 Apr 2019
- 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
- Diagnosis: Chronic myeloid leukemia Myelodysplastic Syndromes Myeloprolipherative neoplsm unclassified Atypical chronic myelogenous leukemia
- Signed informed consent
- Patients with 10/10 HLA-matched 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. Mismatches in these loci are not allowed.
- Peripheral blood stem cells as graft source
- No second tumors
- No prior history of Thymoglobulin exposure or no history of anaphylactic shock after Thymoglobulin administration
- 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.
Russia1 site
First Pavlov State Medical University of St. Petersburg
Saint Petersburg, 197089
About this study
Official title: Randomized Trial of GVHD Prophylasxis With Post-transplantation Cyclophocphomide (PTCy) or Thymoglobulin in Unrelated SCT Recepients With Chronic Myeloproliferative Neoplasms and Myelodisplatic Syndrome
Purpose There is a growing evidence of high efficacy of post-transplantation cyclophocphomide (PTCy)-based GVHD prophylaxis in haploidentical and matched related and unrelated bone marrow transplantation. There is limitted, but growing data on safety and efficacy of this prophylaxis in unrelated and peripheral blood stem cell transplantations. Use of PTCy in chronic myeloproliferative neoplasms and myelodisplatic syndrome is of particular interest. On the one hand, PTCy could reduce the incidence of chronic GVHD and long-term bormidity. On the other hand, there is a concern, that PTCy can increase the incidence of graft failures in this group of patients. Currently published data indicate that low-dose Thymoglobulin-based prophylaxis is the most promissing compatitor in terms of acute and chronic GVHD control. So there is a rationale to randomize Thymoglobulin and PTCy as GVHD prophilaxis. Pre-transplant assesment of moratlity (PAM)-index will be used as the strata for randomization, as it is the paramter that takes into account the most important factors effecting survival. The conditioning regimen and the other two components of GVHD prophylaxis (mycophenolate mofetil and tacrolimus) will be identical in the two arms of the study.
- Conditions
- Leukemia, Chronic Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Being tested
- Unrelated allogeneic stem cell transplantation, Busulfan, Fludarabine monophosphate, Tacrolimus, Mycophenolate mofetil
- Keywords
- Cyclophosphamide, Thymoglobulin, Myelodysplastic Syndromes, Immunosuppressive Agents, Immune System Diseases, Busulfan, Fludarabine, Tacrolimus, Mycophenolate mofetil, Antineoplastic Agents, Alkylating, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic Transplantation, Leukemia, Chronic Myeloid, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unrelated allogeneic stem cell transplantationProcedure or surgery
BusulfanDrug
Fludarabine monophosphateDrug
TacrolimusDrug
CyclophosphamideDrug
ThymoglobulinDrug
| Study group | Role | What they receive |
|---|---|---|
| Thymoglobulin | Experimental | Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -5 Busulfan 1 mg/kg po qid x 2 days Days -4 through -3 Thymoglobulin 2,5 mg/kg po qd x 2 days Days -1 through +30: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days -1 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration Receives: Procedure: Unrelated allogeneic stem cell transplantation; Drug: Busulfan; Drug: Fludarabine monophosphate; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Thymoglobulin |
| PTCy | Experimental | Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration Receives: Procedure: Unrelated allogeneic stem cell transplantation; Drug: Busulfan; Drug: Fludarabine monophosphate; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of primary graft failure
Measured: 60 days
Secondary outcomes (8)
Incidence of acute GVHD, grades II-IV
Measured: 365 days
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Measured: 365 days
Non-relapse mortality analysis
Measured: 365 days
Event-free survival analysis
Measured: 365 days
Overall survival analysis
Measured: 365 days
Relapse rate analysis
Measured: 365 days
Toxicity (NCI CTCAE 4.03)
Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy
Measured: 100 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startJul 2015
- Primary completion3 Apr 2019
- Study completion3 Apr 2019
Why it stopped: Poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Chronic MyeloidStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 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
- Investigators
- Boris V. Afanasyev, Professor, Principal investigator, First Pavlov State Medical University of St. Petersburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02627573
- Sponsor's protocol ID
- 06/15-n
- Status last verified
- Apr 2019
- First submitted
- 4 Dec 2015
- Last updated
- 5 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of GVHD Prophylasxis With Post-transplantation Cyclophocphomide (PTCy) or Thymoglobulin in Unrelated SCT Recepients With Chronic Myeloproliferative Neoplasms and Myelodisplatic Syndrome
- ClinicalTrials.gov ID
- NCT02627573
- Acronym / sponsor ID
- 06/15-n
- Conditions
- Leukemia, Chronic Myeloid, Myelodysplastic Syndromes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Keywords
- Cyclophosphamide, Thymoglobulin, Myelodysplastic Syndromes, Immunosuppressive Agents, Immune System Diseases, Busulfan, Fludarabine, Tacrolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 32 participants (actual)
- Lead sponsor
- St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- 3 Apr 2019 (actual)
- Study completion
- 3 Apr 2019 (actual)
- First posted
- 11 Dec 2015 (estimated)
- 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.
Purpose There is a growing evidence of high efficacy of post-transplantation cyclophocphomide (PTCy)-based GVHD prophylaxis in haploidentical and matched related and unrelated bone marrow transplantation. There is limitted, but growing data on safety and efficacy of this prophylaxis in unrelated and peripheral blood stem cell transplantations. Use of PTCy in chronic myeloproliferative neoplasms and myelodisplatic syndrome is of particular interest. On the one hand, PTCy could reduce the incidence of chronic GVHD and long-term bormidity. On the other hand, there is a concern, that PTCy can increase the incidence of graft failures in this group of patients. Currently published data indicate that low-dose Thymoglobulin-based prophylaxis is the most promissing compatitor in terms of acute and chronic GVHD control. So there is a rationale to randomize Thymoglobulin and PTCy as GVHD prophilaxis. Pre-transplant assesment of moratlity (PAM)-index will be used as the strata for randomization, as it is the paramter that takes into account the most important factors effecting survival. The conditioning regimen and the other two components of GVHD prophylaxis (mycophenolate mofetil and tacrolimus) will be identical in the two arms of the study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thymoglobulin | Experimental | Procedure: Unrelated allogeneic stem cell transplantation, Drug: Busulfan, Drug: Fludarabine monophosphate, Drug: Tacrolimus, Drug: Mycophenolate mofetil, Drug: ThymoglobulinDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -5 Busulfan 1 mg/kg po qid x 2 days Days -4 through -3 Thymoglobulin 2,5 mg/kg po qd x 2 days Days -1 through +30: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days -1 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration |
| PTCy | Experimental | Procedure: Unrelated allogeneic stem cell transplantation, Drug: Busulfan, Drug: Fludarabine monophosphate, Drug: Tacrolimus, Drug: Mycophenolate mofetil, Drug: CyclophosphamideDays -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: 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 (8 listed)
- Patients must have an indication for allogeneic hematopoietic stem cell transplantation
- Diagnosis: Chronic myeloid leukemia Myelodysplastic Syndromes Myeloprolipherative neoplsm unclassified Atypical chronic myelogenous leukemia
- Signed informed consent
- Patients with 10/10 HLA-matched 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. Mismatches in these loci are not allowed.
- Peripheral blood stem cells as graft source
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 |
|---|---|---|
| Unrelated allogeneic stem cell transplantation | Procedure or surgery | PTCy, Thymoglobulin |
| Busulfan | Drug | PTCy, Thymoglobulin |
| Fludarabine monophosphate | Drug | PTCy, Thymoglobulin |
| Tacrolimus | Drug | PTCy, Thymoglobulin |
| Mycophenolate mofetil | Drug | PTCy, Thymoglobulin |
| Cyclophosphamide | Drug | PTCy |
| Thymoglobulin | Drug | Thymoglobulin |
Primary outcome
Incidence of primary graft failure
Time frame: 60 days
8 secondary outcomes
Incidence of acute GVHD, grades II-IV
Time frame: 365 days
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Time frame: 365 days
Non-relapse mortality analysis
Time frame: 365 days
Event-free survival analysis
Time frame: 365 days
Overall survival analysis
Time frame: 365 days
Relapse rate analysis
Time frame: 365 days
Toxicity (NCI CTCAE 4.03)
Time frame: 100 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Time frame: 100 days
Results and safety
The study was stopped early (reason given: Poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Individual participant dataSharing planned: No
Related trials for Leukemia, Chronic Myeloid
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
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
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
Boris V. Afanasyev, Professor principal investigator
First Pavlov State Medical University of St. Petersburg
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 Unrelated allogeneic stem cell transplantation, Busulfan and Fludarabine monophosphate in people with Leukemia, Chronic Myeloid and Myelodysplastic Syndromes, 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: stopped early, as of the sponsor's last update on 5 Apr 2019. 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 was stopped early (reason given: Poor recruitment). Results are not available in the source record.
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 graft failure (time frame: 60 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 5 Apr 2019.