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

Sponsor:	Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):	Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:	NCT00657410

Purpose

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.

Condition	Intervention	Phase
Nonneoplastic Condition	Drug: dexamethasone Drug: prednisone Procedure: quality-of-life assessment	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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.

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia MYH9-related disorder thrombotic thrombocytopenic purpura

Drug Information available for: Dexamethasone Prednisone Dexamethasone acetate Doxiproct plus Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:

Final response (complete, partial, and minimal response) rate from evaluation of initial response [ Time Frame: At day +180 from evaluation of initial response ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Initial response rate [ Time Frame: At day 42 (arm I), at day 46 (arm II) ] [ Designated as safety issue: No ]
Quality of response per arm [ Time Frame: At initial evaluation and at final evaluation ] [ Designated as safety issue: No ]
Final response rate [ Time Frame: At day 180 from the statement of initial response ] [ Designated as safety issue: No ]
Rate of bleeding events [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: Yes ]
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 Frame: At day 42 or before day 180 from the first evaluation ] [ Designated as safety issue: No ]
Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]
Rate of persistent response [ Time Frame: At 12 months from the statement of initial response ] [ Designated as safety issue: No ]
Association of type of initial response with final and persistent response (in patients with final and persistent response) [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]
Rate of rescue interventions [ Time Frame: After day 180 from evaluation of initial response ] [ Designated as safety issue: No ]
Rate of splenectomy eligible patients [ Time Frame: At 12 months from enrollment ] [ Designated as safety issue: No ]
Rate of patients who have undergone splenectomy during follow-up [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]
Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-up [ Time Frame: At 3 years from study entry ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	April 2008
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ARM A - PDN PDN is administered orally at the daily dose of 1 mg/Kg for 4 consecutive weeks (from day 0 to day 28), then, therapy is tapered within 14 days. The patients considered NOT RESPONDER at day 42 or WHO HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be crossed to ARM B.	Drug: prednisone Procedure: quality-of-life assessment
Experimental: ARM B - DXM DXM is administered orally at single fixed daily doses of 40 mg for 4 consecutive days, every 14 days, for 3 consecutive courses. If platelet count is £ 20x109/L or bleeding symptoms related to thrombocytopenia are present, lowdose DXM (0.035 mg/Kg/day) between courses is given. The patients (either from ARM A+B or from ARM B) considered NOT RESPONDER at day 46 or who HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be considered OFF TREATMENT. For these patients a second line therapy will be considered, according to the medical practice of the Centre (splenectomy or other).	Drug: dexamethasone Procedure: quality-of-life assessment

Arms

Assigned Interventions

Experimental: ARM A - PDN

PDN is administered orally at the daily dose of 1 mg/Kg for 4 consecutive weeks (from day 0 to day 28), then, therapy is tapered within 14 days. The patients considered NOT RESPONDER at day 42 or WHO HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be crossed to ARM B.

Drug: prednisone Procedure: quality-of-life assessment

Experimental: ARM B - DXM

DXM is administered orally at single fixed daily doses of 40 mg for 4 consecutive days, every 14 days, for 3 consecutive courses. If platelet count is £ 20x109/L or bleeding symptoms related to thrombocytopenia are present, lowdose DXM (0.035 mg/Kg/day) between courses is given. The patients (either from ARM A+B or from ARM B) considered NOT RESPONDER at day 46 or who HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be considered OFF TREATMENT.

For these patients a second line therapy will be considered, according to the medical practice of the Centre (splenectomy or other).

Drug: dexamethasone Procedure: quality-of-life assessment

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of primary immune thrombocytopenic purpura (ITP)
- Newly diagnosed, previously untreated disease
Meets 1 of the following criteria:
- Platelet count ≤ 20,000/mm³
- Platelet count > 20,000/mm³ and < 50,000/mm³ plus bleeding symptom score ≥ 8
  - Patients with bleeding score 15 due to intracranial hemorrhage or GI bleeding are not eligible
Unconfirmed diagnosis of primary ITP not allowed if any of the following criteria are met:
- Positivity of any of the following autoimmunity markers:
  - Antinuclear antibody ≥ 1:80
  - Antithyroglobulin, antitireoperoxidase, anticardiolipin antibodies (GP-I ≥ 40 U/mL)
  - Anti-β2glycoprotein antibodies (IgG ≥ 40 U/mL)
  - Lupus anticoagulant (Kaolin clotting time [KCT] ratio, dilute Russell's viper venom time [dRVVT] ratio ≥ 1.5 times the upper limit of normal [ULN])
  - Direct antiglobulin test
- Presence of autoimmune hemolytic anemia
- Presence of connective tissue disease

PATIENT CHARACTERISTICS:

Not pregnant or nursing
No active malignancy at time of study entry
No cardiovascular diseases requiring treatment
No severe non-controlled, despite therapy, hypertension and diabetes
No active gastric ulcer
Creatinine ≤ 2 times ULN
ALT and AST ≤ 2 times ULN
No hepatitis C virus antibody, HIV antibody, hepatitis B surface antigen, or hepatitis B core antibody seropositive status
No chronic liver disease
No concomitant severe psychiatric disorders
No documented viral illness as evidenced by positivity of IgM
No IgM positivity for patients who had vaccination 1 months before diagnosis

PRIOR CONCURRENT THERAPY:

At least 5 days since prior steroids
- Steroid therapy (equivalent doses of prednisone ≤ 1 mg/kg/day) < 2 days before randomization allowed
No initiation of new drug within one week before diagnosis
No concurrent anti-platelet and/or anticoagulant drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657410

Locations

Italy
U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico	Recruiting
Tricase, (le), Italy
Contact: Vincenzo PAVONE, Pr. salentoematologia@piafondazionepanico.it
Principal Investigator: Vincenzo PAVONE, Pr.
SOC EMATOLOGIA ASO SS Antonio e Biagio	Recruiting
Alessandria, Italy
Contact: Alessandro LEVIS alevis@ospedale.al.it
Principal Investigator: Alessandro LEVIS, Pr.
Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"	Recruiting
Ascoli, Italy
Contact: Piero GALIENI, Pr. p.galieni@asl13.marche.it
Principal Investigator: Piero GALIENI, Pr.
UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari	Recruiting
Bari, Italy
Contact: Rita RIZZI, dr ritarizzi@ematba.uniba.it
Principal Investigator: Rita RIZZI, Dr.
Ospedali Riuniti di Bergamo	Recruiting
Bergamo, Italy, 24100
Contact: Alessandro Rambaldi, MD 39-35-269491
Principal Investigator: Alessandro RAMBALDI, Pr.
University of Bologna Medical School	Recruiting
Bologna, Italy, 40138
Contact: Nicola VIANELLI, Dr. nicola.vianelli@unibo.it
Sezione di Ematologia e Trapianti Spedali Civili	Recruiting
Brescia, Italy, 21125
Contact: Giuseppe ROSSI rossig@med.unibs.it
Principal Investigator: Giuseppe ROSSI, Pr.
Struttura Complessa di Oncologia Medica - Azienda Ospedaliera - Ospedale di Circolo di Busto Arsizio	Recruiting
Busto Arsizio, Italy
Contact: Giorgio REGUZZONI, Dr. greguzzoni@ao.busto.it
Principal Investigator: Luigi MONTALBETTI, Dr.
Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile	Recruiting
Civitanova - Marche, Italy
Contact: Riccardo CENTURIONI, Dr. ricentu@tin.it
Principal Investigator: Riccardo CENTURIONI, Dr.
Sub-Investigator: Rosanna RE, Dr.
U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza	Recruiting
Cosenza, Italy
Contact: Fortunato MORABITO, Dr. fortunato_morabito@tin.it
Principal Investigator: Fortunato MORABITO, Dr.
Sub-Investigator: Brigida GULINO, Dr.
Ospedale Maggiore - Div.Medicina Crema	Recruiting
Crema, Italy
Contact: Gianfrancesco FIORINI, Pr. medicina2@hcrema.it
Principal Investigator: Gianfrancesco FIORINI, Pr.
Ospedali Riuniti Foggia	Recruiting
Foggia, Italy, 71100
Contact: Silvana Franca CAPALBO, Dr. scapalbo@ospedaliriunitifoggia.it
Principal Investigator: Silvana Franca CAPALBO, Dr.
Ospedale Santa Maria Goretti	Recruiting
Latina, Italy, 04100
Contact: Giuseppe CIMINO, Pr. cimino@bce.uniroma1.it
Principal Investigator: Giuseppe CIMINO, Pr.
ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia	Recruiting
Lecce, Italy, 73100
Contact: Nicola DI RENZO direnzo.ematolecce@libero.it
Principal Investigator: Nicola DI RENZO, Dr.
Sub-Investigator: Claudia QUINTAVALLE, Dr.
Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST	Recruiting
Meldola, Italy
Contact: Dino AMADORI, Dr. direzione.scientifica@irst.emr.it
Principal Investigator: Dino AMADORI, Dr.
Azienda Ospedaliera San Paolo - Unità di Ematologia e Trombosi	Recruiting
Milano, Italy
Contact: Marco CATTANEO, Dr. marco.cattaneo@unimi.it
Principal Investigator: Marco CATTANEO, Dr.
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro	Recruiting
Novara, Italy
Contact: Gianluca GAIDANO, Dr. gaidano@med.unipmn.it
Contact: Monia LUNGHI, Dr.
Principal Investigator: Gianluca GAIDANO, Pr.
Sub-Investigator: Monia LUNGHI, Dr.
Cattedra di Ematologia CTMO Università degli Studi di Parma	Recruiting
Parma, Italy
Contact: Cecilia CARAMATTI, Dr. cecilia.caramatti@unipr.it
Principal Investigator: Cecilia CARAMATTI, Dr.
Sub-Investigator: Elena ROSETTI, Dr.
Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo	Recruiting
Pavia, Italy, 27100
Contact: Patrizia NORIS p.noris@smatteo.pv.it
Principal Investigator: Patrizia NORIS, Dr.
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza	Recruiting
Piacenza, Italy
Contact: Daniele VALLISA, Dr. d.vallisa@ausl.pc.it
Principal Investigator: Daniele VALLISA, Dr.
Sub-Investigator: Elena TRABACCHI, Dr.
Pordenone Unità operativa Medicina II Az. Osp. S. M. degli Angeli	Recruiting
Pordenone, Italy
Contact: Luigi VIRGOLINI, Pr. luigi.virgolini@aopn.fvg.it
Principal Investigator: Luigi VIRGOLINI, Dr.
Ospedale S. M. delle Croci	Recruiting
Ravenna, Italy, I-48100
Contact: Luigi VIRGOLINI, Dr. luigi.virgolini@aopn.fvg.it
Principal Investigator: Luigi VIRGOLINI, Dr.
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"	Recruiting
Reggio Calabria, Italy
Contact: Francesco NOBILE, Pr. f.nobile@netonline.it
Principal Investigator: NOBILE, Pr.
Sub-Investigator: Donatella VINCELLI, Dr.
Arcispedale S. Maria Nuova	Recruiting
Reggio Emilia, Italy, 42100
Contact: Francesco MERLI, Pr. francesco.merli@asmn.re.it
Principal Investigator: Francesco MERLI, Dr.
Ospedale "Infermi"	Recruiting
Rimini, Italy
Contact: Pier Paolo FATTORI, Pr. pfattori@auslrn.net
Principal Investigator: Pier Paolo FATTORI, Pr.
Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia	Recruiting
Roma, Italy
Contact: Bruno MONARCA, Pr. b.monarca@libero.it
Principal Investigator: Bruno MONARCA, Pr.
Sub-Investigator: Antonella FERRARI, Dr.
Divisione di Ematologia - Ospedale S. Camillo	Recruiting
Roma, Italy
Contact: Ignazio MAJOLINO, Pr. imajolino@scamilloforlanini.rm.it
Principal Investigator: Ignazio MAJOLINO, Pr.
University Campus Bio-Medico	Recruiting
Rome, Italy, 00155
Contact: Giuseppe Avvisati, MD, PhD 39-6-2254-11
Principal Investigator: Giuseppe AVVISATI, Pr.
UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"	Recruiting
Rome, Italy, 00161
Contact: Maria Gabriella MAZZUCCONI, Pr. 39-06-4424-1984 mazzucconi@bce.uniroma.it
Principal Investigator: Maria Gabriella MAZZUCCONI, Pr.
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Recruiting
Rome, Italy, 00168
Contact: Valerio DE STEFANO, Dr. valerio.destefano@rm.unicatt.it
Principal Investigator: Valerio DE STEFANO, Dr.
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza	Recruiting
San Giovanni Rotondo, Italy
Contact: Nicola CASCAVILLA, Pr. n.cascavilla@operapadrepio.it
Principal Investigator: Nicola CASCAVILLA, Pr.
.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"	Recruiting
Siena, Italy
Contact: Francesco LAURIA, Pr. lauria@unisi.it
Principal Investigator: Francesco LAURIA, Pr.
SCDO Ematologia 2 AOU Giovanni Battista	Recruiting
Torino, Italy
Contact: Mario BOCCADORO, Pr. mario.boccadoro@unito.it
Principal Investigator: Mario BOCCADORO, Pr.
Struttura Complessa II Medicina - Ematologia - Centro di Riferimento Ematologico - Ospedale Maggiore	Recruiting
Trieste, Italy
Contact: Gabriele POZZATO g.pozzato@fmc.units.it
Principal Investigator: Gabriele POZZATO, Pr.
Sub-Investigator: Stefano BONETTO, Dr.
Policlinico G. B. Rossi - Borgo Roma	Recruiting
Verona, Italy, 37134
Contact: Giovanni Pizzolo, MD giovanni.pizzolo@univr.it
Principal Investigator: Giovanni PIZZOLO, Pr.
Sub-Investigator: Dino DE VENERI, Dr.
Ospedale San Bortolo	Recruiting
Vicenza, Italy, 36100
Contact: Francesco RODEGHIERO, Pr. rodeghiero@hemato.ven.it
Principal Investigator: Cicenzo RODEGHIERO, Pr.

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Principal Investigator:

Maria Gabriella Mazzucconi, MD

Gruppo Italiano Malattie EMatologiche dell'Adulto

Responsible Party:	Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:	NCT00657410 History of Changes
Other Study ID Numbers:	ITP0207, GIMEMA-ITP-0207, Eudract 2008-000417-30, EU-20839
Study First Received:	April 11, 2008
Last Updated:	November 9, 2011
Health Authority:	Italy: Ethics Committee