Infliximab in Treating Patients With Myelodysplastic Syndrome

July 13, 2012 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Randomized Phase II Trial With Infliximab (Remicade) in Patients With Myelodysplastic Syndrome and a Relatively Low Risk of Developing Acute Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium, 8000
        • AZ Sint-Jan
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Brussels, Belgium, 1070
        • Hopital Universitaire Erasme
      • Edegem, Belgium, B-2650
        • Universitair Ziekenhuis Antwerpen
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
      • Roeselare, Belgium, 8800
        • H. Hartziekenhuis - Roeselaere.
      • Verviers, Belgium, B-4800
        • Centre Hospitalier Peltzer-La Tourelle
  • Czech Republic
      • Olomouc, Czech Republic, 775 20
        • University Hospital - Olomouc
      • Prague, Czech Republic, 128 20
        • Institute of Hematology and Blood Transfusion
  • France
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75181
        • Hotel Dieu de Paris
  • Germany
      • Heidelberg, Germany, D-69117
        • Ruprecht - Karls - Universitaet Heidelberg
      • Stuttgart, Germany, 70199
        • Marienhospital Stuttgart
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
  • Italy
      • Pesaro, Italy, I-61100
        • Ospedale San Salvatore
  • Netherlands
      • Amsterdam, Netherlands, 1007 MB
        • Vrije Universiteit Medisch Centrum
      • Den Haag, Netherlands, 2597AX
        • Ziekenhuis Bronovo
      • Leiden, Netherlands, 2300 RC
        • Leiden University Medical Center
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis (within the past month) of low- or intermediate-risk myelodysplastic syndromes (MDS) meeting all of the following criteria:

    • No more than 10% bone marrow blasts (corresponding to refractory anemia [RA], RA with ringed sideroblasts, or RA with excess blasts)

    • Meets at least 1 of the following hematopoietic criteria:

      • Hemoglobin no greater than 10 g/dL OR red blood cell transfusion dependent
      • Neutrophil count no greater than 1,500/mm^3
      • Platelet count no greater than 100,000/mm^3 OR platelet transfusion dependent

    • No poor cytogenetics (complex abnormalities or involvement of chromosome 7)

      • Patients with unknown cytogenetics may be eligible provided reasonable efforts have been made for determining the cytogenetic profile and the results are considered a failure (e.g., normal karyotype [NN] with no more than 10 metaphases)

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Best response as measured by Cheson response criteria

Secondary Outcome Measures

Outcome Measure
Duration of highest grade toxicity as assessed by CTCAE v3.0 after response

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Heinz Zwierzina, MD, Medical University Innsbruck

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Primary Completion (Actual)

December 1, 2006

Study Registration Dates

First Submitted

December 10, 2003

First Submitted That Met QC Criteria

December 10, 2003

First Posted (Estimate)

December 11, 2003

Study Record Updates

Last Update Posted (Estimate)

July 16, 2012

Last Update Submitted That Met QC Criteria

July 13, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-06023

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on infliximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe