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

NCT01345708 | Completed Phase 2 DMC

• 1 other identifier: Eudra CT 2008-006713-25
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Autoimmune Hemolytic Disease (Cold Type) (Warm Type)

Keywords

Low dose rituximab; WAIHA; CHD

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Sustained response (SR)

  month +6, month +12

Interventions

prednisone, low dose rituximab DRUG

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• University Hospital, Udine, Italy: collaborator

Study Sites (2)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Wilma Barcellini MD, UO Ematologia 2, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Related Publications (4)

• 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. doi: 10.3324/haematol.11709.

  PMID: 18055995 BACKGROUND

• 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.

  PMID: 20546023 BACKGROUND

• Gomez-Almaguer D, Solano-Genesta M, Tarin-Arzaga L, Herrera-Garza JL, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Jaime-Perez 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.

  PMID: 20841509 BACKGROUND

• Barcellini W, Zaja F, Zaninoni A, Imperiali FG, Battista ML, Di Bona E, Fattizzo B, Consonni D, Cortelezzi A, Fanin R, Zanella A. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies. Blood. 2012 Apr 19;119(16):3691-7. doi: 10.1182/blood-2011-06-363556. Epub 2012 Jan 20.

  PMID: 22267606 DERIVED

MeSH Terms

Interventions

Prednisone; Rituximab

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• PierMannuccio Mannucci, MD

  Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 28 20122, Milano.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 28, 2011
• First Posted: May 2, 2011
• Study Start: January 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2011
• Last Updated: May 2, 2011

Record last verified: 2011-04

Locations

IT (2)