Therapy of Chronic Cold Agglutinin Disease With Eculizumab (DECADE)

• ClinicalTrials.gov Identifier: NCT01303952
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Last Update Posted: July 19, 2017
• Sponsor: University Hospital, Essen
• Collaborator: Alexion
• Information provided by (Responsible Party): Alexander Roeth, MD, University Hospital, Essen

Study Description

Brief Summary:

Evaluation of the efficacy and safety of eculizumab in symptomatic or transfusion-dependent patients with untreated or refractory hemolytic cold agglutinin disease(CAD)

Condition or disease	Intervention/treatment	Phase
Cold Agglutinin Disease	Drug: Eculizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-Randomized Multi-Center Study Demonstrating the Efficacy of Terminal Complement Inhibition in Patients With Cold Agglutinin Disease Using Eculizumab
• Actual Study Start Date: January 2011
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eculizumab	Drug: Eculizumab; Weekly treatment with eculizumab (600 mg) via IV infusion for 4 doses followed the next week by eculizumab (900 mg) IV infusion and maintenance treatment with Eculizumab (900 mg) via IV infusion every other week for 21 weeks

Outcome Measures

Primary Outcome Measures :

1. LDH [ Time Frame: From baseline to 26 weeks ]
   Primary endpoint for this study is: lactate dehydrogenase (LDH) in U/l change from baseline to 26 weeks

Secondary Outcome Measures :

1. Transfusion avoidance [ Time Frame: From baseline to 26 weeks ]
2. PRBC units transfused [ Time Frame: From baseline to 26 weeks ]
3. Change in hemoglobin levels [ Time Frame: From baseline to 26 weeks ]
4. Haptoglobin [ Time Frame: From baseline to 26 weeks ]
5. Hemopexin [ Time Frame: From baseline to 26 weeks ]
6. Free hemoglobin [ Time Frame: From baseline to 26 weeks ]
7. Reticulocytes [ Time Frame: From baseline to 26 weeks ]
8. SF-36v2 QLQ [ Time Frame: From baseline to 26 weeks ]
9. FACIT-F SCALE version 4 [ Time Frame: From baseline to 26 weeks ]
10. Six-Minute Walk Test [ Time Frame: From baseline to 26 weeks ]
11. Circulatory symptoms [ Time Frame: From baseline to 26 weeks ]
12. Thrombosis record [ Time Frame: From baseline to 26 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Individuals at least 18 years of age
• Diagnosis of CAD defined by the combination of chronic hemolysis, cold agglutinin titer (IgM or IgA) >64 at 4°C, positive direct antiglobulin test (DAT) when performed with polyspecific antiserum, negative (or only weakly positive) anti-IgG, and strongly positive with anti-C3d
• LDH level > 2 x upper limit of normal (ULN)
• Clinical symptoms requiring treatment, such as anemia, anemia-related symptoms or hemolysis-related symptoms
• Sufficient supplementation of iron, folic acid and vitamin B12 prior to treatment phase
• Patient must be willing and able to give written informed consent;
• Patients must be vaccinated against N. meningitidis at least 14 days prior treatment
• Patient must avoid conception during the trial using a method that is most appropriate for their physical state and culture

Exclusion Criteria:

• Active aggressive lymphoma requiring therapy or an active non-lymphatic malignant disease other than basal cell carcinoma or CIS of the cervix
• Liver disease with elevated LDH
• Absolute neutrophil count < 500/µL
• Presence or suspicion of active bacterial or viral infection, in the opinion of the Investigator, at treatment start or severe recurrent bacterial infections
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
• Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-treatment Phase
• History of bone marrow/stem cell transplantation
• Inability to cooperate or any condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study
• Hypersensitivity to eculizumab, to murine proteins or to one of the excipients

Contacts and Locations

Locations

Germany

Department of Hematology, University Hospital Essen

Essen, Germany, 45122

Sponsors and Collaborators

University Hospital, Essen

Alexion

Investigators

• Principal Investigator: Alexander Roeth, MD; Department of Hematology, University Hospital Essen

More Information

Publications:

Roth A, Huttmann A, Rother RP, Duhrsen U, Philipp T. Long-term efficacy of the complement inhibitor eculizumab in cold agglutinin disease. Blood. 2009 Apr 16;113(16):3885-6. doi: 10.1182/blood-2009-01-196329. No abstract available.

Roth A, Duhrsen U. Cold agglutinin disease. Eur J Haematol. 2010 Jan 1;84(1):91. doi: 10.1111/j.1600-0609.2009.01320.x. Epub 2009 Jul 14. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roth A, Bommer M, Huttmann A, Herich-Terhurne D, Kuklik N, Rekowski J, Lenz V, Schrezenmeier H, Duhrsen U. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018 Oct 9;2(19):2543-2549. doi: 10.1182/bloodadvances.2018024190.

• Responsible Party: Alexander Roeth, MD, MD, University Hospital, Essen
• ClinicalTrials.gov Identifier: NCT01303952
• Other Study ID Numbers: CAD01; 2009-016966-97 ( EudraCT Number )
• First Posted: February 25, 2011
• Last Update Posted: July 19, 2017
• Last Verified: July 2017

Keywords provided by Alexander Roeth, MD, University Hospital, Essen:

cold agglutinin disease; hemolysis; eculizumab; terminal complement inhibition

Additional relevant MeSH terms:

Hematologic Diseases; Autoimmune Diseases; Immune System Diseases; Anemia, Hemolytic, Autoimmune; Anemia, Hemolytic; Anemia; Eculizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs