FIBRAPLO - Haplo-identical transplantation in patients with myleofibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Feb 2021 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ESTEVE · MEDAC

External identifiers

EU CT number

2024-513325-23-00

EudraCT number

2019-003216-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective is disease-free survival and without rejection one year after haplo-identical transplantation in patients with primary or secondary myelofibrosis.

Secondary objectives 13

1. -incidence of acute GVHD grade 2/4 at 100 days
2. -incidence of acute GVHD grade 3/4 at 100 days
3. engraftment at 100 days
4. incidence of chronic GVHD at 12 months
5. non-relapse mortality at 12 months
6. overall survival at 12 months
7. relapse/progression incidence at 12 months
8. rejection incidence at 12 months
9. time to neutrophil engraftment at 60 days
10. time to platelet engraftment at 100 days
11. infection incidence at 100 days and at 12 months
12. -cytokine profile during transplantation
13. impact of genetic alterations on outcome

Conditions and MedDRA coding

Myelofibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1.  Patients aged between 18 and 70 years
2.  Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia Vera proven by marrow biopsy
3. The myelofibrosis should combine at least 2 of the following criteria: o constitutional symptoms: weight loss > 10% in one year, fever (without infection), recurrent muscle, bone or join pains, extreme fatigue o anemia with hemoglobin < 10 gr/dL or red blood cell transfusion requirement o thrombocytopenia < 100 G/L o peripheral blast count > 1% at least found 2 times o white blood cell count > 25 G/L (before a cytoreductive treatment) o Karyotype: +8, -7/7q-, i(17q), -5, 5q-, 12p-, inv(3), 11q23
4.  Performance status according to ECOG at 0, 1 or 2
5.  With health insurance coverage
6.  Having signed a written informed consent
7.  Women agreed to take nomegestrol acetate as contraception during and up to 6 months after treatment by treosulfan
8.  Men agreed not to conceive child during and up to 6 months after treatment by treosulfan

Exclusion criteria 12

1.  Myelofibrosis transformed into acute leukemia
2.  Poor performance status with ECOG 3 or more
3.  Cardiac failure with EF < or = 50% currently or in the past (even if corrected after treatment)
4.  Renal failure with creatininemia > 130 µmol/L or clearance < 50ml/min
5.  Respiratory function altered with vital capacity < 70% or forced expired volume < 70%
6.  Biological significant liver abnormalities; ASAT or ALAT> 2 x normal range, bilirubin > 1,5 x normal range
7.  HLA matched donor available
8.  Tutorship or curatorship
9.  Unwilling or unable to comply with the protocol
10.  Pregnant woman or breastfeeding
11.  Contraindications to treosulfan o Hypersensitivity to the active substance o Active non-controlled infectious disease o Fanconi anaemia and other DNA breakage repair disorders o Administration of live vaccine
12.  Contraindications or any circumstance that precludes the use of the drugs involved in the protocol (especially Thiotepa and Fludarabine)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main criteria of judgement is disease- and rejection-free survival 12 months after HSCT.

Secondary endpoints 11

1. incidence of acute grade 2-4 and grade 3-4 GVHD according to the modified Glucksberg classification
2. incidence of chronic GVHD (limited vs extensive) at 12 months according to the revised Seattle criteria
3. neutrophil engraftment on day 60 post-transplantation, 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
4. latelet recovery: first day of platelet > 20G/L without transfusion the last 7 days assessed on day 100
5. overall survival at 12 months
6. on-relapse mortality at 12 months
7. incidence of relapse/progression at 12 months
8. incidence of rejection at 12 months
9. infection incidence at 100 days, 12 months (annexe for infection)
10. cytokine profile during transplantation (day-7 +/- 1 jour, J0 and day J7 +/- 1 jour )
11. impact of genetic alterations on overall survival at 12 months and non-relapse mortality at 12 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr. Marie ROBIN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr. Marie ROBIN

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications