MyelofibrosisPhase 2FIBRAPLONCT04728490
Haplo-identical Transplantation in Patients With Myelofibrosis - A Phase 2 Prospective Multicentric Prospective Study
A Phase 2 study testing Allogenic transplantation transplantation in people with Myelofibrosis, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
The only curative treatment in patients with primary or secondary myelofibrosis is allogeneic hematopoietic stem cells (HSCT). It has been reported that intermediate and higher risk patients according to international prognostic scores benefit from HSCT in terms of survival (Kröger et al, 2015). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- Allogenic transplantation transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- 30 Jan 2021to 30 Jan 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 aged between 18 and 70 years
- Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia Vera proven by marrow biopsy
- The myelofibrosis should combine at least 2 of the following criteria:
- constitutional symptoms: weight loss > 10% in one year, fever (without infection), recurrent muscle, bone or join pains, extreme fatigue
- anemia with hemoglobin < 10 gr/dL or red blood cell transfusion requirement
- thrombocytopenia < 100 G/L
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- peripheral blast count > 1% at least found 2 times
- white blood cell count > 25 G/L (before a cytoreductive treatment)
- Karyotype: +8, -7/7q-, i(17q), -5, 5q-, 12p-, inv(3), 11q23
- Performance status according to ECOG at 0, 1 or 2
- With health insurance coverage
- Having signed a written informed consent
- Women agreed to take nomegestrol acetate as contraception during and up to 6 months after treatment by treosulfan
- Men agreed not to conceive child during and up to 6 months after treatment by treosulfan
Who cannot join
- Myelofibrosis transformed into acute leukemia
- Poor performance status with ECOG 3 or more
- Cardiac failure with EF < or = 50% currently or in the past (even if corrected after treatment)
- Renal failure with creatininemia > 130 µmol/L or clearance < 50ml/min
- Respiratory function altered with vital capacity < 70% or forced expired volume < 70%
- Biological significant liver abnormalities; ASAT or ALAT> 2 x normal range, bilirubin > 1,5 x normal range
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- HLA matched donor available
- Tutorship or curatorship
- Unwilling or unable to comply with the protocol
- Pregnant woman or breastfeeding
- Contraindications to treosulfan
- Hypersensitivity to the active substance
- Active non-controlled infectious disease
- Fanconi anaemia and other DNA breakage repair disorders
- Administration of live vaccine
- Contraindications or any circumstance that precludes the use of the drugs involved in the protocol (especially Thiotepa and Fludarabine)
Trial locations and contacts
No sites are listed yet.
About this study
The only curative treatment in patients with primary or secondary myelofibrosis is allogeneic hematopoietic stem cells (HSCT). It has been reported that intermediate and higher risk patients according to international prognostic scores benefit from HSCT in terms of survival (Kröger et al, 2015). In 2013, we conducted in France a prospective trial testing the use of ruxolitinib before transplantation ("JAK-ALLO study" NCT01795677). Outcome of patients was better in patients transplanted with a matched sibling donor than an unrelated donor confirming other studies (Kröger et al, 2009; Rondelli et al, 2014). In the JAK-ALLO trial, acute GVHD incidence was high, often hyperacute and severe. Recently, the EBMT group has reported a registry study on familial haplo-identical transplantation (haplo) in patients with myelofibrosis (Raj et al, 2018). Post-transplant cyclophosphamide was used in 59% of cases. One-year overall survival (OS) and disease-free survival (DFS) were 61 and 58% which favorably compared to outcome after unrelated transplantation. Genova team has also reported impressive results after haplo-identical transplantation in their center (Bregante et al, 2015). Bregante et al have reported outcome of 2 cohorts transplanted from 2000 to 2010 and from 2011 to 2014. The main difference between the 2 periods is the more frequent use of haplo in the second period (54% versus 5%). Outcome was much better in the second period with OS at 70% versus 49% and authors suggest that this improvement is related to the best outcome among haplo transplantation. The improvement of outcome after haplo has been attributed to a better GVHD prophylaxis, especially with the use of post-transplant cyclophosphamide. Given the poor outcome after unrelated transplantation and especially in HLA mismatched unrelated setting and encouraging results in family haplo identical transplantation, this current study proposes to test haplo-identical transplantation in myelofibrosis patients without a matched related donor.
The main objective of this study is disease and rejection-free survival one year after haplo-identical transplantation in patients with primary or secondary myelofibrosis.
- Conditions
- Myelofibrosis
- Being tested
- Allogenic transplantation transplantation
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic transplantation transplantationOther
Haplo-identical transplantation with the use of Treosulfan, Thiotepa and Fludarabine in conditioning regimen.
| Study group | Role | What they receive |
|---|---|---|
| Allogenic transplantation using treosulfan in conditioning regimen | Experimental | Haplo-identical transplantation using treosulfan in conditioning regimen Treosuflan, in the conditioning regimen will be administrated as followed 10 gr/m2 per day -4, -3 and -2 IV route
In combination with:
Thiotepa 5 mg/kg on day -6 Fludarabine 30 mg/m2 per day from day -5 to day -1 Receives: Other: Allogenic transplantation transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease and rejection free survival
Measured: 12 months after haplo-identical transplantation
Secondary outcomes (14)
Incidence of acute GVHD grade 2/4
Acute GVHD will be assessed according to the modified Glucksberg classification
Measured: at 100 days
Incidence of acute GVHD grade 3 or 4
Acute GVHD will be assessed according to the modified Glucksberg classification
Measured: at 100 days
Engraftment
Engraftment is defined as neutrophil engraftment : neutrophil count at 0.5G/L or higher for more than 3 consecutive days after transplantation, it should be confirmed by a donor chimerism and platelet recovery: platelet engraftment will be defined as first day of platelet > 20G/L without transfusion the last 7 days assessed on day 100
Measured: at 100 days
Incidence of chronic GVHD
Chronic GVHD will be assessed according to the revised Seattle criteria
Measured: at 12 months
Non-relapse mortality
Measured: at 12 months
Overall survival
Measured: at 12 months
Relapse incidence
Measured: at 12 months
Rejection incidence
Measured: at 12 months
Time to neutrophil engraftment
Neutrophil engraftment is defined as neutrophil count at 0.5G/L or higher for more than 3 consecutive days after transplantation, it should be confirmed by a donor chimerism
Measured: at 100 days
Time to platelet engraftment
Platelet engraftment is defined as first day of platelet > 20G/L without transfusion the last 7 days assessed on day 100
Measured: at 100 days
Infection incidence
Measured: at 100 days
Infection incidence
Measured: at 12 months
Cytokine profile during transplantation
Measured: day-6
Cytokine profile during transplantation
Measured: at day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2021
- Study start30 Jan 2021 (estimated)
- Primary completion30 Jan 2024 (estimated)
- Study completion30 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04728490
- Sponsor's protocol ID
- APHP190648
- Acronym
- FIBRAPLO
- Status last verified
- Jan 2021
- First submitted
- 24 Jan 2021
- Last updated
- 28 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haplo-identical Transplantation in Patients With Myelofibrosis - A Phase 2 Prospective Multicentric Prospective Study
- ClinicalTrials.gov ID
- NCT04728490
- Acronym / sponsor ID
- FIBRAPLO / APHP190648
- Conditions
- Myelofibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 30 Jan 2021 (estimated)
- Primary completion
- 30 Jan 2024 (estimated)
- Study completion
- 30 Jan 2024 (estimated)
- First posted
- 28 Jan 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.
The only curative treatment in patients with primary or secondary myelofibrosis is allogeneic hematopoietic stem cells (HSCT). It has been reported that intermediate and higher risk patients according to international prognostic scores benefit from HSCT in terms of survival (Kröger et al, 2015). In 2013, we conducted in France a prospective trial testing the use of ruxolitinib before transplantation ("JAK-ALLO study" NCT01795677). Outcome of patients was better in patients transplanted with a matched sibling donor than an unrelated donor confirming other studies (Kröger et al, 2009; Rondelli et al, 2014). In the JAK-ALLO trial, acute GVHD incidence was high, often hyperacute and severe. Recently, the EBMT group has reported a registry study on familial haplo-identical transplantation (haplo) in patients with myelofibrosis (Raj et al, 2018). Post-transplant cyclophosphamide was used in 59% of cases. One-year overall survival (OS) and disease-free survival (DFS) were 61 and 58% which favorably compared to outcome after unrelated transplantation. Genova team has also reported impressive results after haplo-identical transplantation in their center (Bregante et al, 2015). Bregante et al have reported outcome of 2 cohorts transplanted from 2000 to 2010 and from 2011 to 2014. The main difference between the 2 periods is the more frequent use of haplo in the second period (54% versus 5%). Outcome was much better in the second period with OS at 70% versus 49% and authors suggest that this improvement is related to the best outcome among haplo transplantation. The improvement of outcome after haplo has been attributed to a better GVHD prophylaxis, especially with the use of post-transplant cyclophosphamide. Given the poor outcome after unrelated transplantation and especially in HLA mismatched unrelated setting and encouraging results in family haplo identical transplantation, this current study proposes to test haplo-identical transplantation in myelofibrosis patients without a matched related donor.
The main objective of this study is disease and rejection-free survival one year after haplo-identical transplantation in patients with primary or secondary myelofibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogenic transplantation using treosulfan in conditioning regimen | Experimental | Other: Allogenic transplantation transplantationHaplo-identical transplantation using treosulfan in conditioning regimen Treosuflan, in the conditioning regimen will be administrated as followed 10 gr/m2 per day -4, -3 and -2 IV route In combination with: Thiotepa 5 mg/kg on day -6 Fludarabine 30 mg/m2 per day from day -5 to day -1 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients aged between 18 and 70 years
- Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia Vera proven by marrow biopsy
- The myelofibrosis should combine at least 2 of the following criteria:
- Performance status according to ECOG at 0, 1 or 2
- With health insurance coverage
Key exclusion criteria (16 listed)
- Myelofibrosis transformed into acute leukemia
- Poor performance status with ECOG 3 or more
- Cardiac failure with EF < or = 50% currently or in the past (even if corrected after treatment)
- Renal failure with creatininemia > 130 µmol/L or clearance < 50ml/min
- Respiratory function altered with vital capacity < 70% or forced expired volume < 70%
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 |
|---|---|---|
| Allogenic transplantation transplantationHaplo-identical transplantation with the use of Treosulfan, Thiotepa and Fludarabine in conditioning regimen. | Other | Allogenic transplantation using treosulfan in conditioning regimen |
Primary outcome
Disease and rejection free survival
Time frame: 12 months after haplo-identical transplantation
14 secondary outcomes
Incidence of acute GVHD grade 2/4
Time frame: at 100 days
Incidence of acute GVHD grade 3 or 4
Time frame: at 100 days
Engraftment
Time frame: at 100 days
Incidence of chronic GVHD
Time frame: at 12 months
Non-relapse mortality
Time frame: at 12 months
Overall survival
Time frame: at 12 months
Relapse incidence
Time frame: at 12 months
Rejection incidence
Time frame: at 12 months
Time to neutrophil engraftment
Time frame: at 100 days
Time to platelet engraftment
Time frame: at 100 days
Infection incidence
Time frame: at 100 days
Infection incidence
Time frame: at 12 months
Cytokine profile during transplantation
Time frame: day-6
Cytokine profile during transplantation
Time frame: at day 0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Myelofibrosis
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RecruitingPhase 3
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
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RecruitingObservational study
Motor Development and Early Predictors of Psychomotor Outcomes in Preterm and Term Infants Assessed by MOS-R and Caregiver Questionnaire at 18 and 36 Months
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Active, not recruitingPhase 3
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Myelofibrosis
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogenic transplantation transplantation in people with Myelofibrosis, run by Assistance Publique - Hôpitaux de Paris.
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 14 inclusion and 16 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 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
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 Marie Robin, Dr (+331-42-49-47-24, marie.robin@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease and rejection free survival (time frame: 12 months after haplo-identical transplantation). 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 Jan 2021.