A Single-Arm Pilot Study With Low-Dose Rituximab Plus Standard Oral Prednisone In Idiopathic Autoimmune Hemolytic Anemia

Autoimmune Hemolytic Disease (Cold Type) (Warm Type) Clinical Trial

Official title:

A Single-Arm Pilot Study With Low-Dose Rituximab Plus Standard Oral Prednisone In Idiopathic Autoimmune Hemolytic Anemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01345708
• Other study ID #: Eudra CT 2008-006713-25
• Status: Completed
• Phase: Phase 2
• First received: April 28, 2011
• Last updated: April 29, 2011
• Start date: January 2009
• Est. completion date: January 2011

Study information

• Verified date: April 2011
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The aim of this prospective study was to evaluate the activity, safety and the duration of the response of low dose rituximab associated with standard oral prednisone as first line therapy in newly diagnosed warm autoimmune hemolytic anemia and cold hemagglutinin disease, and as second line therapy in warm autoimmune hemolytic anemia relapsed after standard oral prednisone. Further aim was to correlate the clinical response to biological parameters (cytokine and anti-erythrocyte antibody production in cultures).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly diagnosed "warm" or "cold" AIHA, defined by symptomatic anemia and positive DAT, in the absence of underlying lymphoproliferative, infectious or neoplastic disease (according to the single Center diagnostic criteria).

• Idiopathic "warm" or "cold" AIHA relapsed after first line treatment with oral prednisone.

• Aged >18 years

• ECOG performance status grade 0, 1 or 2

• No psychiatric illness that precludes understanding concepts of the trial or signing informed consent

• Patients who have provided written informed consent prior to study participation, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.

Exclusion Criteria:

• Cell or humoral immunologic deficit (congenital or acquired)

• Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

• Active bacterial, viral, or fungal infection requiring systemic therapy HIV or HbsAg positive (with HBV-DNA+) or HCV-Ab positive (with HCV-RNA+) patients

• History of malignancies within 3 years prior to study entry

• Concomitant immunosuppressive or cytotoxic treatment

• Positive pregnancy test. Lactation.

• The presence of associated organ-specific autoimmune diseases do not constitute exclusion criteria. Previous splenectomy does not constitute exclusion criteria

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Disease (Cold Type) (Warm Type)
• Hemolysis

Intervention

Drug:
• prednisone, low dose rituximab
Patients with "warm" AIHA will receive: Rituximab 100 mg i.v.weekly (fixed dose irrespective of body surface area) for 4 consecutive weeks (days +7, +14, +21, +28), and prednisone 1 mg/kg/die p.o. days from day +1 to day +30, followed by tapering (10 mg/week until 0.5/mg/kg/die, then 5 mg/week until stop) Patients with CHD will receive: Rituximab 100 mg i.v.weekly (fixed dose irrespective of body surface area) for 4 consecutive weeks (days +7, +14, +21, +28)

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	MIlan
Italy	Wilma Barcellini MD, UO Ematologia 2, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milan

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Ospedale	University Hospital, Udine, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Gómez-Almaguer D, Solano-Genesta M, Tarín-Arzaga L, Herrera-Garza JL, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, Jaime-Pérez JC. Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias. Blood. 2010 Dec 2;116(23):4783-5. doi: 10.1182/blood-2010-06-291831. Epub 2010 Sep 14. — View Citation

Provan D, Butler T, Evangelista ML, Amadori S, Newland AC, Stasi R. Activity and safety profile of low-dose rituximab for the treatment of autoimmune cytopenias in adults. Haematologica. 2007 Dec;92(12):1695-8. — View Citation

Zaja F, Vianelli N, Volpetti S, Battista ML, Defina M, Palmieri S, Bocchia M, Medeot M, De Luca S, Ferrara F, Isola M, Baccarani M, Fanin R. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010 Oct;85(4):329-34. doi: 10.1111/j.1600-0609.2010.01486.x. Epub 2010 Jul 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response	Response will be evaluated at each clinic visit. Complete response (CR) will be defined as Hb increase >2 g/dL and Hb > 12 g/dL, normalization of all haemolytic markers and no transfusion requirement;Partial response (PR) will be defined as Hb increase >2 g/dL and Hb 10-12 g/dL, and 50% reduction of transfusion. In the remaining cases there is no response.	month +2	Yes
Secondary	Sustained response (SR)	Sustained response (SR) was defined as Hb > 10 g/dL at month +6 and +12, in the absence of any treatment.	month +6, month +12	Yes