Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 to 80	Other	GIMEMA-ITP-0207 GIMEMA-ITP-0207, Eudract 2008-000417-30, EU-20839, NCT00657410

Objectives

Primary

1. 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

1. Compare rate of initial response.
2. Compare quality of response.
3. Compare rate of final responses and rate of persistent response.
4. Compare rate of bleeding events.
5. Determine rate of resumed response with HD-DXM in non-responder patients or patients who have lost response (arm I only).
6. Compare time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms.
7. Compare rate of rescue interventions.
8. Compare rate of eligible patients for splenectomy.
9. Compare rate of patients who underwent splenectomy.
10. Compare rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others).
11. Compare patient’s self reported quality of life.

Entry 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

Prior/Concurrent Therapy:

• At least 2 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

Patient Characteristics:

• Not pregnant or nursing
• No active malignancy at time of study entry
• No hypertension, cardiovascular diseases, or diabetes requiring treatment
• 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

Expected Enrollment

Outcomes

Final response (complete, partial, and minimal response) rate at day 180 from evaluation of initial response

Initial response rate at day 42 (arm I), at day 46 (arm II)
Quality of response per arm at initial evaluation and at final evaluation
Final response rate at day 180 from the statement of initial response
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 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)
Rate of rescue interventions after day 180 from evaluation of initial response
Rate of splenectomy eligible patients at 12 months from enrollment
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

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 Contact Information

Trial Lead Organizations

Gruppo Italiano Malattie Ematologiche dell’Adulto

Maria Gabriella Mazzucconi, MD, Principal investigator		Ph: 39-06-4424-1984

Italy
	Rome
	Gruppo Italiano Malattie Ematologiche dell’Adulto
		Contact Person	Ph:  39-06-4424-1984
			Email: mazzucconi@bce.uniroma.it

Registry 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.
Trial Start Date		2008-04-01
Registered in ClinicalTrials.gov		NCT00657410
Date Submitted to PDQ		2008-03-28
Information Last Verified		2008-04-10

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