Prednisone or Dexamethasone in Treating Patients With Newly Diagnosed, Previously Untreated Primary Immune Thrombocytopenic Purpura

Condition(s) targeted: Nonneoplastic Condition

Intervention: dexamethasone (Drug); prednisone (Drug); quality-of-life assessment (Procedure)

Phase: Phase 3

Status: Recruiting

Sponsored by: Gruppo Italiano Malattie EMatologiche dell'Adulto

Official(s) and/or principal investigator(s):
Maria Gabriella Mazzucconi, MD, Principal Investigator, Affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto

RATIONALE: Drugs, such as prednisone and dexamethasone, may change the immune system and be an effective treatment for primary immune thrombocytopenic purpura. It is not yet known which drug is more effective in treating primary immune thrombocytopenic purpura.

PURPOSE: This randomized phase III trial is studying high-dose dexamethasone to see how well it works compared to standard-dose prednisone in treating patients with newly diagnosed, previously untreated primary immune thrombocytopenic purpura.

Official title: Randomized Study of the Treatment of Primary Immune Thrombocytopenic Purpura (ITP) in Newly Diagnosed Untreated Adult Patients. Comparison of Standard Dose Prednisone Versus High-dose Dexamethasone.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Final response (complete, partial, and minimal response) rate from evaluation of initial response

Secondary outcome:

Initial response rate

Quality of response per arm

Final response rate

Rate of bleeding events

Resumed response rate in non-responder patients (at day 42) or patients who have lost response before day 180 from the first evaluation (arm I only)

Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms

Rate of persistent response

Association of type of initial response with final and persistent response (in patients with final and persistent response)

Rate of rescue interventions

Rate of splenectomy eligible patients

Rate of patients who have undergone splenectomy during follow-up

Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-up

Detailed description: OBJECTIVES:

Primary

- To evaluate the role of therapy intensification in adult patients with newly diagnosed,

previously untreated primary immune thrombocytopenic purpura with high-dose dexamethasone (HD-DXM), in terms of improvement of response at 6 months after initial response, in comparison with standard-doses of prednisone.

Secondary

- Compare rate of initial response.

- Compare quality of response.

- Compare rate of final responses and rate of persistent response.

- Compare rate of bleeding events.

- Determine rate of resumed response with HD-DXM in non-responder patients or patients

who have lost response (arm I only).

- Compare time to platelet number increase until a hemostatically effective level is

reached and/or disappearance of bleeding symptoms.

- Compare rate of rescue interventions.

- Compare rate of eligible patients for splenectomy.

- Compare rate of patients who underwent splenectomy.

- Compare rate of patients who develop connective tissue diseases or underlying

hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others).

- Compare patient's self reported quality of life.

OUTLINE: This is a multicenter study. Patients are stratified by treating center. Patients are randomized to 1 of 2 treatment arms.

- Arm I (Standard-dose prednisone): Patients receive oral prednisone at a standard dose

(1 mg/Kg) once daily on days 1-28 followed by a 14-day taper.

Patients considered non-responders at day 42 or who have lost response before evaluation of final response (day 180) are crossed to arm II.

- Arm II (High-dose dexamethasone): Patients receive oral dexamethasone at a high dose

(40 mg/day) once daily on days 1-4. Treatment repeats every 14 days for 3 courses.

Quality of life is assessed at baseline, on day 42 (arm I) or 46 (arm II) (initial response evaluation day), 180 days after initial response evaluation, and at 3, 9, 12 months after randomization.

After completion of study treatment, patients are followed monthly until 1 year after randomization, every 2 months for 1 year, and then every 3 months for 1 year.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion criteria

- Signed written informed consent according to IGH/EU/GCP and national local laws

- Newly diagnosed untreated ITP adult patients

- Age > 18 < 80 years

- Platelet count <20x109/L

- Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to

grading scale at paragraph 7. 1)

- Baseline Quality of Life evaluation questionnaire filled in Newly diagnosed untreated

ITP adult patients

- Age > 18 < 80 years

- Platelet count <20x109/L

- Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to

grading scale at paragraph 7. 1)

- Baseline Quality of Life evaluation questionnaire filled in

Exclusion criteria

- Active malignancy at time of study entry

- Steroids administration (PDN <1mg/Kg/day) for more than 5 days before randomization

- Concomitant treatment with anti-platelet and or anti-coagulant drugs

- Concomitant severe psychiatric disorders

- Not confirmed diagnosis of ITP for

- *Positivity of autoimmunity markers: antinucleus (≥1: 80), anti-tireoglobulin,

anti-tireoperoxidase, anti-cardiolipin (≥ 40 GPL UmL), anti-b2glycoprotein (≥ 40 IgG U/mL) antibodies, Lupus Anticoagulant (KCT ratio, dRVVT ratios ≥1. 5 times the upper normal limit ), direct antiglobulin test (DAT ).

- Presence of autoimmune hemolytic anemia

- Presence of connective tissue disease

- Women who are pregnant or breastfeeding

- Cardiovascular diseases requiring treatment

- Severe non-controlled, despite therapy, hypertension and diabetes

- Liver and kidney function impairment (creatinine, ALT, AST >2 times upper normal

limit)

- HCVAb, HIVAb, HBsAg, HBcAb seropositive status

- Chronic liver disease

- Documented viral illness by the positivity of IgM, or vaccination both occurred one

month before diagnosis

- Intake of drugs not previously taken within one week before diagnosis

- Bleeding score 15 due to ICH or to GI bleeding (according to grading scale at

paragraph 7. 1, Tab. 3)

- Active gastric ulcer.

Azienda ospedaliera Nuovo Ospedale "Torrette", Ancona, Italy; Recruiting
Pietro Leoni, Email: pleoni@univpm.it
Pietro Leoni, Pr., Principal Investigator

USL 8 - Ospedale S.Donato, Arezzo, Italy; Recruiting
Antonio Benci, Dr., Email: ematolar@virgilio.it
Antonio Benci, Dr., Principal Investigator

UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari, Bari, Italy; Recruiting
Rita RIZZI, dr, Email: ritarizzi@ematba.uniba.it
Rita RIZZI, Dr., Principal Investigator

Ospedali Riuniti di Bergamo, Bergamo 24100, Italy; Recruiting
Alessandro Rambaldi, MD, Phone: 39-35-269491
Alessandro RAMBALDI, Pr., Principal Investigator

University of Bologna Medical School, Bologna 40138, Italy; Recruiting
Nicola VIANELLI, Dr., Email: nicola.vianelli@unibo.it
Nicola Vianelli, Dr., Principal Investigator
Riccardo Ragionieri, Dr., Sub-Investigator

Sezione di Ematologia e Trapianti Spedali Civili, Brescia 21125, Italy; Recruiting
Giuseppe ROSSI, Email: rossig@med.unibs.it
Giuseppe ROSSI, Pr., Principal Investigator

Struttura Complessa di Oncologia Medica - Azienda Ospedaliera - Ospedale di Circolo di Busto Arsizio, Busto Arsizio, Italy; Recruiting
Marco Bregni, Dr., Email: mbregni@aobusto.it
Marco Bregni, Dr., Principal Investigator

Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile, Civitanova - Marche, Italy; Recruiting
Riccardo CENTURIONI, Dr., Email: ricentu@tin.it
Riccardo CENTURIONI, Dr., Principal Investigator
Rosanna RE, Dr., Sub-Investigator

U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza, Cosenza, Italy; Recruiting
Fortunato MORABITO, Dr., Email: fortunato_morabito@tin.it
Fortunato MORABITO, Dr., Principal Investigator
Brigida GULINO, Dr., Sub-Investigator

Ospedale Santa Maria Goretti, Latina 04100, Italy; Recruiting
Giuseppe CIMINO, Pr., Email: cimino@bce.uniroma1.it
Giuseppe CIMINO, Pr., Principal Investigator

ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia, Lecce 73100, Italy; Recruiting
Nicola DI RENZO, Email: direnzo.ematolecce@libero.it
Nicola DI RENZO, Dr., Principal Investigator
Claudia QUINTAVALLE, Dr., Sub-Investigator

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina, Messina, Italy; Recruiting
Caterina Musolino, Pr., Email: cmusolino@unime.it
Caterina Musolino, Pr., Principal Investigator
Alessandro Allegra, Dr., Sub-Investigator

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro, Novara, Italy; Recruiting
Gianluca GAIDANO, Dr., Email: gaidano@med.unipmn.it
Monia LUNGHI, Dr.
Gianluca GAIDANO, Pr., Principal Investigator
Monia LUNGHI, Dr., Sub-Investigator

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone", Palermo, Italy; Recruiting
Gerlando Quintini, Dr., Email: gerlando.quintini@libero.it
Gerlando Quintini, Dr., Principal Investigator

Cattedra di Ematologia CTMO Università degli Studi di Parma, Parma, Italy; Recruiting
Cecilia CARAMATTI, Dr., Email: cecilia.caramatti@unipr.it
Cecilia CARAMATTI, Dr., Principal Investigator
Elena ROSETTI, Dr., Sub-Investigator

Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo, Pavia 27100, Italy; Recruiting
Patrizia NORIS, Email: p.noris@smatteo.pv.it
Patrizia NORIS, Dr., Principal Investigator

U.O. Ematologia Clinica - Azienda USL di Pescara, Pescara, Italy; Recruiting
Giuseppe Fioritoni, Dr., Email: gfioritoni@tin.it
Giuseppe Fioritoni, Dr., Principal Investigator

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza, Piacenza, Italy; Recruiting
Daniele VALLISA, Dr., Email: d.vallisa@ausl.pc.it
Daniele VALLISA, Dr., Principal Investigator
Elena TRABACCHI, Dr., Sub-Investigator

Pordenone Unità operativa Medicina II Az. Osp. S. M. degli Angeli, Pordenone, Italy; Recruiting
Luigi VIRGOLINI, Pr., Email: luigi.virgolini@aopn.fvg.it
Luigi VIRGOLINI, Dr., Principal Investigator
Anna Ermacora, Dr., Sub-Investigator

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli", Reggio Calabria, Italy; Recruiting
Francesco NOBILE, Pr., Email: f.nobile@netonline.it
NOBILE, Pr., Principal Investigator
Donatella VINCELLI, Dr., Sub-Investigator

Ospedale "Infermi", Rimini, Italy; Recruiting
Patrizia Tosi, Dr., Email: patrizia.tosi@auslrn.net
Patrizia Tosi, Dr., Principal Investigator

Divisione di Ematologia - Ospedale S. Camillo, Roma, Italy; Recruiting
Ignazio MAJOLINO, Pr., Email: imajolino@scamilloforlanini.rm.it
Ignazio MAJOLINO, Pr., Principal Investigator

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia, Roma, Italy; Recruiting
Bruno MONARCA, Pr., Email: b.monarca@libero.it
Bruno MONARCA, Pr., Principal Investigator
Antonella FERRARI, Dr., Sub-Investigator

UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza", Rome 00161, Italy; Recruiting
Maria Gabriella MAZZUCCONI, Pr., Phone: 39-06-4424-1984, Email: mazzucconi@bce.uniroma.it
Maria Gabriella MAZZUCCONI, Pr., Principal Investigator

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore, Rome 00168, Italy; Recruiting
Giuseppe Leone, Pr., Email: gleone@rm.unicatt.it
Giuseppe Leone, Pr., Principal Investigator

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Recruiting
Nicola CASCAVILLA, Pr., Email: n.cascavilla@operapadrepio.it
Nicola CASCAVILLA, Pr., Principal Investigator

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte", Siena, Italy; Recruiting
Francesco LAURIA, Pr., Email: lauria@unisi.it
Francesco LAURIA, Pr., Principal Investigator
Marzia Defina, Dr., Sub-Investigator

Struttura Complessa II Medicina - Ematologia - Centro di Riferimento Ematologico - Ospedale Maggiore, Trieste, Italy; Recruiting
Giorgio Paladini, Pr., Email: giorgio.paladini@aots.sanita.fvg.it
Giorgio Paladini, Pr., Principal Investigator
Stefano BONETTO, Dr., Sub-Investigator

Policlinico G. B. Rossi - Borgo Roma, Verona 37134, Italy; Recruiting
Giovanni Pizzolo, MD, Email: giovanni.pizzolo@univr.it
Giovanni PIZZOLO, Pr., Principal Investigator
Dino DE VENERI, Dr., Sub-Investigator

Ospedale San Bortolo, Vicenza 36100, Italy; Recruiting
Francesco RODEGHIERO, Pr., Email: rodeghiero@hemato.ven.it
Cicenzo RODEGHIERO, Pr., Principal Investigator
Stefania Fortuna, Dr., Sub-Investigator

U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico, Tricase, (le), Italy; Recruiting
Vincenzo PAVONE, Pr., Email: salentoematologia@piafondazionepanico.it
Vincenzo PAVONE, Pr., Principal Investigator

Starting date: April 2008
Last updated: June 6, 2012