Haplo-identical Transplantation in Patients With Myelofibrosis - A Phase 2 Prospective Multicentric Prospective Study

Myelofibrosis Clinical Trial

— FIBRAPLO  

Official title:

Haplo-identical Transplantation in Patients With Myelofibrosis - A Phase 2 Prospective Multicentric Prospective Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04728490
• Other study ID #: APHP190648
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 30, 2021
• Est. completion date: January 30, 2024

Study information

• Verified date: January 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Marie Robin, Dr
• Phone: +331-42-49-47-24
• Email: marie.robin[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 28
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

• 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

Exclusion Criteria:

• 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

• 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)

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Other:
• Allogenic transplantation transplantation
Haplo-identical transplantation with the use of Treosulfan, Thiotepa and Fludarabine in conditioning regimen.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease and rejection free survival		12 months after haplo-identical transplantation
Secondary	Incidence of acute GVHD grade 2/4	Acute GVHD will be assessed according to the modified Glucksberg classification	at 100 days
Secondary	Incidence of acute GVHD grade 3 or 4	Acute GVHD will be assessed according to the modified Glucksberg classification	at 100 days
Secondary	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	at 100 days
Secondary	Incidence of chronic GVHD	Chronic GVHD will be assessed according to the revised Seattle criteria	at 12 months
Secondary	Non-relapse mortality		at 12 months
Secondary	Overall survival		at 12 months
Secondary	Relapse incidence		at 12 months
Secondary	Rejection incidence		at 12 months
Secondary	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	at 100 days
Secondary	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	at 100 days
Secondary	Infection incidence		at 100 days
Secondary	Infection incidence		at 12 months
Secondary	Cytokine profile during transplantation		day-6
Secondary	Cytokine profile during transplantation		at day 0