Study to Compare Busulfan-fludarabine With Thiotepa-fludarabine Regimen in Allogeneic Transplantation for Myelofibrosis

NCT01814475 | Completed Phase 2 DMC

• 1 other identifier: 2010-022052-23 GITMO - MF2010
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 21

Brief Summary

This study will be performed as a prospective multicenter phase II trial for compare busulfan-fludarabine reduced-intensity conditioning (RIC) with thiotepa-fludarabine RIC regimen prior to allogeneic transplantation of hematopoietic cells for the treatment of myelofibrosis. The primary endpoint for this study is to compare Progression Free Survival of two different RIC regimens for allogeneic stem cell transplantation in myelofibrosis. Progression Free Survival is defined as the time from the date of randomization to the date of the first documented disease progression or relapse (according to the International Working Group Consensus Criteria) or death due to any cause. Patients who have neither progressed nor died at the time of study completion or who are lost to follow-up are censored at the data of the last follow up for progression of disease for this study.

Conditions

Myelofibrosis

Keywords

myelofibrosis; unfavourable prognostic factors; Allogeneic stem cell transplantation; Progression Free Survival; thrombocythemia vera; polycythemia vera; Reduced-intensity conditioning

Outcome Measures

Primary Outcomes (1)

• Progression -free survival at one year

  The primary endpoint for this study is to compare Progression Free Survival of two different RIC regimens for allogeneic stem cell transplantation in myelofibrosis. Progression Free Survival is defined as the time from the date of randomization to the date of the first documented disease progression or relapse (according to the International Working Group Consensus Criteria) or death due to any cause. Patients who have neither progressed nor died at the time of study completion or who are lost to follow-up are censored at the data of the last follow up for progression of disease for this study.

  Assessment at 1 year post randomization

Secondary Outcomes (7)

• Safety and efficacy profile: The non relapse mortality

  Assessment at 1 year post randomization

• Safety and efficacy profile: Overall survival

  Assessment at 1 year post randomization

• Safety and efficacy profile: responses

  Assessment at 1 year post randomization

• Safety and efficacy profile: molecular remissions

  Assessment at 1 year post randomization

• Safety and efficacy profile: engraftment

  participants will be followed for the duration of hospital stay, an expected average of 30 days

Study Arms (2)

A: Fludarabine + Busulphan

ACTIVE COMPARATOR

Conventional conditioning regimen with Fludarabine and Busulphan (Busilvex)for allogeneic stem cell transplantation in myelofibrosis

Drug: A: Fludarabine + Busulphan

B: Fludarabine + Thiotepa

EXPERIMENTAL

Reduced-intensity conditioning with Fludarabine and Thiotepa for allogeneic stem cell transplantation in myelofibrosis

Drug: B: Fludarabine + Thiotepa

Interventions

A: Fludarabine + Busulphan DRUG

Fludarabine 30 mg/m2/d, day -8 to day-3 and Busulphan (Busilvex) 0,8 mg/Kg/i.v. dose x 4 doses on days -5,-4 and x 2 doses on day -3, total dose 8 mg/Kg) prior allogenic transplant (day zero)

Also known as: BU-FLU

A: Fludarabine + Busulphan

B: Fludarabine + Thiotepa DRUG

Fludarabine 30 mg/m2/d day -8 to day -3 Thiotepa 6 mg/Kg for 2 doses ( days -4, -3) prior allogeneic transplant (day zero)

Also known as: THIO-FLU

B: Fludarabine + Thiotepa

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 ≤ 70 years
• Primary or secondary myelofibrosis after essential thrombocythemia or polycythemia vera
• One of the following unfavourable prognostic factors: Hb \< 10 g/dL or leukocytes \>25x109/L or \> 1% circulating blasts in the peripheral blood or constitutional symptoms
• Performance Status (Karnofsky)≥ 60%
• Hematopoietic Cell Transplantation Comorbidity Score ≤ 5
• Written informed consent

You may not qualify if:

• ≥ 20% blasts in peripheral blood and/or bone marrow
• Positive serologic markers for human immunodeficiency virus (HIV)
• Acute hepatitis B virus (HBV) or acute hepatic C virus (HCV) infection
• Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as: --total bilirubin, Serum Glutamate Oxaloacetate Transaminase (SGOT) or Serum Glutamate Pyruvate Transaminase (SGPT) \> 5 the upper normal limit;
• Left ventricular ejection fraction \< 40%;
• Clearance creatinine \< 30 ml/min;
• Diffusing Capacity of Lung for Carbon monoxide (DLCO) \< 30% and/or receiving supplementary oxygen.
• Pregnancy or lactation
• Any active, uncontrolled infection
• Donors:
• Age ≥ 18 \< 65 years
• human leukocyte antigen (HLA)-identical sibling donor by high resolution DNA-based HLA-A, -B, -C, -DRB1, typing
• human leukocyte antigen (HLA)-identical unrelated donor by high resolution DNA-based human leukocyte antigen-A, human leukocyte antigen-B, human leukocyte antigen-C, human leukocyte antigen-DRB1 typing. One allele mismatched (class I) can be accepted for recipients up to 60 years.

Sponsors & Collaborators

• Gruppo Italiano Trapianto di Midollo Osseo: lead

Study Sites (21)

Azienda Ospedaliera SS Antonio e Biagio

Alessandria, Italy

Location

Clinica di Ematologia - Ospedali Riuniti di Ancona

Ancona, Italy

Location

Divisione di Ematologia - Ospedali Papa Giovanni XXIII

Bergamo, Italy

Location

AO Spedali Civili di Brescia- USD - TMO Adulti

Brescia, Italy

Location

Ospedale Ferrarotto - Ematologia

Catania, Italy

Location

Cattedra di Ematologia - Azienda Ospedaliera di Careggi

Florence, Italy

Location

Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza

Foggia, Italy

Location

AOU IRCCS San Martino - IST

Genova, Italy

Location

Ospedale Panico

Lecce, Italy

Location

Divisione di Ematologia - Istituto Nazionale dei Tumori

Milan, Italy

Location

Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -

Modena, Italy

Location

AO Ospedali Riuniti Villa Sofia - Cervello

Palermo, Italy

Location

Dipartimento Oncologico La Maddalena

Palermo, Italy

Location

Fondazione IRCCS San Matteo

Pavia, 27100, Italy

Location

Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara

Pescara, Italy

Location

Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli

Reggio Calabria, Italy

Location

Arciospedale S. M. Novella

Reggio Emilia, Italy

Location

Cattedra di Ematologia - Università La Sapienza

Roma, Italy

Location

Ospedale San Giuseppe Moscato

Taranto, Italy

Location

Ematologia 2 - ASO San Giovanni Battista

Torino, Italy

Location

A.O. Santa Maria della Misericordia

Udine, Italy

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera

Interventions

Busulfan; Thiotepa

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Francesca Patriarca, MD

  Azienda Ospedaliera Santa Maria della Misericordia di Udine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 20, 2013
• Study Start: July 1, 2011
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: August 20, 2021

Record last verified: 2021-08

Locations

IT (21)