Prednisone or Dexamethasone in Newly Diagnosed, Previously Untreated Primary Immune Thrombocytopenic Purpura (ITP0207)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00657410
First received: April 11, 2008
Last updated: July 14, 2016
Last verified: July 2016
  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 3

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:


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 ]

Enrollment: 150
Study Start Date: April 2008
Estimated Study Completion Date: December 2016
Primary Completion Date: February 2016 (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

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   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Tricase, (le), Italy
S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Azienda ospedaliera Nuovo Ospedale "Torrette"
Ancona, Italy
USL 8 - Ospedale S.Donato
Arezzo, Italy
Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
Ascoli, Italy
UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari
Bari, Italy
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
University of Bologna Medical School
Bologna, Italy, 40138
Sezione di Ematologia e Trapianti Spedali Civili
Brescia, Italy, 21125
Struttura Complessa di Oncologia Medica - Azienda Ospedaliera - Ospedale di Circolo di Busto Arsizio
Busto Arsizio, Italy
Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile
Civitanova - Marche, Italy
U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza
Cosenza, Italy
Ospedale Maggiore - Div.Medicina Crema
Crema, Italy
Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
Foggia, Italy
Ospedale Santa Maria Goretti
Latina, Italy, 04100
ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia
Lecce, Italy, 73100
Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
Meldola, Italy
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
Messina, Italy
Azienda Ospedaliera San Paolo - Unità di Ematologia e Trombosi
Milano, Italy
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
Novara, Italy
Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
Palermo, Italy
Cattedra di Ematologia CTMO Università degli Studi di Parma
Parma, Italy
Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo
Pavia, Italy, 27100
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy
Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
Piacenza, Italy
Pordenone Unità operativa Medicina II Az. Osp. S. M. degli Angeli
Pordenone, Italy
Dipartimento Oncologico - Ospedale S.Maria delle Croci
Ravenna, Italy
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
Reggio Emilia, Italy
Ospedale "Infermi"
Rimini, Italy
Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
Roma, Italy
Divisione Ematologia - Università Campus Bio-Medico
Roma, Italy
Divisione di Ematologia - Ospedale S. Camillo
Roma, Italy
UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"
Rome, Italy, 00161
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy, 00168
Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy
U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
Siena, Italy
Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino"
Torino, Italy
Struttura Complessa II Medicina - Ematologia - Centro di Riferimento Ematologico - Ospedale Maggiore
Trieste, Italy
Clinica Ematologica - Policlinico Universitario
Udine, Italy
Policlinico G. B. Rossi - Borgo Roma
Verona, Italy, 37134
Ospedale San Bortolo
Vicenza, Italy, 36100
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Maria Gabriella Mazzucconi, MD Gruppo Italiano Malattie EMatologiche dell'Adulto
  More Information

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: July 14, 2016
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
idiopathic thrombocytopenic purpura

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on July 28, 2016