Infliximab in Treating Patients With Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00074074
First received: December 10, 2003
Last updated: July 13, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Biological: infliximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial With Infliximab (Remicade) in Patients With Myelodysplastic Syndrome and a Relatively Low Risk of Developing Acute Leukemia

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Best response as measured by Cheson response criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of highest grade toxicity as assessed by CTCAE v3.0 after response [ Designated as safety issue: Yes ]

Enrollment: 46
Study Start Date: October 2003
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074074

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

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00074074     History of Changes
Other Study ID Numbers: EORTC-06023, EORTC-06023
Study First Received: December 10, 2003
Last Updated: July 13, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014