Infliximab in Treating Patients With Myelodysplastic Syndrome

NCT ID: NCT00074074

Last Updated: 2012-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31

Brief Summary

RATIONALE: Monoclonal antibodies, such as infliximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Randomized phase II trial to study the effectiveness of infliximab in treating patients who have myelodysplastic syndrome.

Detailed Description

OBJECTIVES:

• Determine the therapeutic activity of 2 different doses of infliximab on peripheral blood cell count and peripheral and bone marrow blast cell count in patients with low- or intermediate-risk myelodysplastic syndromes.
• Determine the subjective and objective toxicity of these regimens in these patients.
• Determine the response rates (complete and partial response and hematological improvement) in patients treated with these regimens.
• Determine the duration of response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to cytogenetics (good vs intermediate vs unknown due to failure), overall International Prognostic Scoring System score (low [0] vs intermediate 1 [0.5-1.0] vs intermediate 2 [1.5-2.0]), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive infliximab IV on days 1, 15, 43, 71, 99, 127, 155, and 183 in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive a higher dose of infliximab as in arm I. Patients achieving response (complete or partial response or hematological improvement) continue therapy beyond day 183 in the absence of disease progression.

Patients are followed at 2 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this study within 2 years.

Conditions

Myelodysplastic Syndromes

Keywords

refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; previously treated myelodysplastic syndromes

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

infliximab

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• No history of documented hepatitis C
• No documented active hepatitis B
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT less than 2.5 times ULN

Renal

• Creatinine less than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease
• No clinical history or evidence of congestive heart failure
• No severe cardiac dysfunction
• LVEF greater than 35%

Pulmonary

• No prior or concurrent active or latent tuberculosis (TB)

• No evidence of prior or concurrent active TB (i.e., fibrotic or pleural scarring, pulmonary nodules, mediastinal and/or hilar lymphadenopathy, upper lobe volume loss, or cavitation) by chest x-ray
• Negative intradermal tuberculin skin test (i.e., induration less than 5 mm)
• No severe pulmonary dysfunction

Immunologic

• No prior or concurrent opportunistic infection (e.g., herpes zoster, cytomegalovirus, Pneumocystic carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within the past 6 months
• No concurrent severe (CTC grade III or IV) active, chronic, or recurrent infections
• No recent history of allergies
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No prior clinically significant adverse event to murine or chimeric proteins or human/murine recombinant products
• No recent contact with an individual with active TB
• No poor medical risk due to other systemic disease
• No multiple sclerosis or other demyelinating disorder
• No peripheral neuropathy greater than CTC grade 1
• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior infliximab or other monoclonal antibodies
• At least 6 weeks since prior hematopoietic growth factors for MDS
• At least 3 months since prior therapy targeted at reducing tumor necrosis factor (TNF) alpha (e.g., pentoxifylline, thalidomide, or etanercept)
• No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
• No other concurrent drugs targeted at reducing TNF alpha (e.g., pentoxifylline, thalidomide, or etanercept)

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• No prior solid organ transplantation

• Corneal transplantation more than 3 months ago allowed

Other

• No prior randomization to this clinical trial
• At least 6 weeks since prior treatment for MDS (except supportive care)
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent therapeutic-dose nonsteroidal anti-inflammatory drugs (NSAIDs)

• Concurrent sporadic (no more than 3 tablets/week) over-the-counter NSAIDs allowed
• Concurrent cardioprotective doses (80 mg/day or equivalent) of aspirin allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heinz Zwierzina, MD

Role: STUDY_CHAIR

Medical University Innsbruck

Locations

AZ Sint-Jan

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

H. Hartziekenhuis - Roeselaere.

Roeselare, , Belgium

Centre Hospitalier Peltzer-La Tourelle

Verviers, , Belgium

University Hospital - Olomouc

Olomouc, , Czechia

Institute of Hematology and Blood Transfusion

Prague, , Czechia

Centre Antoine Lacassagne

Nice, , France

Hotel Dieu de Paris

Paris, , France

Ruprecht - Karls - Universitaet Heidelberg

Heidelberg, , Germany

Marienhospital Stuttgart

Stuttgart, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Ospedale San Salvatore

Pesaro, , Italy

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Ziekenhuis Bronovo

The Hague, , Netherlands

Countries

Belgium; Czechia; France; Germany; Italy; Netherlands

References

Baron F, Suciu S, Amadori S, Muus P, Zwierzina H, Denzlinger C, Delforge M, Thyss A, Selleslag D, Indrak K, Ossenkoppele G, de Witte T. Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group. Haematologica. 2012 Apr;97(4):529-33. doi: 10.3324/haematol.2011.044347. Epub 2011 Nov 18.

Reference Type: RESULT

PMID: 22102701 (View on PubMed)

Baila L, Suciu S, Muus P, et al.: Assessment of two doses of infliximab in patients with low/intermediate risk IPSS myelodysplastic syndrome (MDS): an EORTC leukemia group (LG) randomized phase II trial (06023). [Abstract] Blood 110 (11): A-1456, 2007.

Reference Type: RESULT

Other Identifiers

EORTC-06023

Identifier Type: -

Identifier Source: secondary_id

EORTC-06023

Identifier Type: -

Identifier Source: org_study_id