Overview

This trial is active, not recruiting.

Condition nonneoplastic condition
Treatments dexamethasone, prednisone, quality-of-life assessment
Phase phase 3
Sponsor Gruppo Italiano Malattie EMatologiche dell'Adulto
Start date April 2008
End date February 2016
Trial size 150 participants
Trial identifier NCT00657410, EU-20839, Eudract 2008-000417-30, GIMEMA-ITP-0207, ITP0207

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
prednisone
quality-of-life assessment
(Experimental)
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).
dexamethasone
quality-of-life assessment

Primary Outcomes

Measure
Final response (complete, partial, and minimal response) rate from evaluation of initial response
time frame: At day +180 from evaluation of initial response

Secondary Outcomes

Measure
Initial response rate
time frame: At day 42 (arm I), at day 46 (arm II)
Quality of response per arm
time frame: At initial evaluation and at final evaluation
Final response rate
time frame: At day 180 from the statement of initial response
Rate of bleeding events
time frame: At 3 years from study entry
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
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
Rate of persistent response
time frame: At 12 months from the statement of initial response
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
Rate of rescue interventions
time frame: After day 180 from evaluation of initial response
Rate of splenectomy eligible patients
time frame: At 12 months from enrollment
Rate of patients who have undergone splenectomy during follow-up
time frame: At 3 years from study entry
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

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

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.

Additional Information

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.
Principal investigator Maria Gabriella Mazzucconi, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Gruppo Italiano Malattie EMatologiche dell'Adulto.