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Infliximab in Treating Patients With Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
infliximab
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • AZ Sint-Jan
  • Institut Jules Bordet
  • Hopital Universitaire Erasme
  • Universitair Ziekenhuis Antwerpen
  • U.Z. Gasthuisberg
  • H. Hartziekenhuis - Roeselaere.
  • Centre Hospitalier Peltzer-La Tourelle
  • University Hospital - Olomouc
  • Institute of Hematology and Blood Transfusion
  • Centre Antoine Lacassagne
  • Hotel Dieu de Paris
  • Ruprecht - Karls - Universitaet Heidelberg
  • Marienhospital Stuttgart
  • Southwest German Cancer Center at Eberhard-Karls-University
  • Ospedale San Salvatore
  • Vrije Universiteit Medisch Centrum
  • Ziekenhuis Bronovo
  • Leiden University Medical Center
  • Universitair Medisch Centrum St. Radboud - Nijmegen

Outcomes

Primary Outcome Measures

Best response as measured by Cheson response criteria

Secondary Outcome Measures

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

Full Information

First Posted
December 10, 2003
Last Updated
July 13, 2012
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00074074
Brief Title
Infliximab in Treating Patients With Myelodysplastic Syndrome
Official Title
Randomized Phase II Trial With Infliximab (Remicade) in Patients With Myelodysplastic Syndrome and a Relatively Low Risk of Developing Acute Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
December 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
infliximab
Primary Outcome Measure Information:
Title
Best response as measured by Cheson response criteria
Secondary Outcome Measure Information:
Title
Duration of highest grade toxicity as assessed by CTCAE v3.0 after response

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heinz Zwierzina, MD
Organizational Affiliation
Medical University Innsbruck
Official's Role
Study Chair
Facility Information:
Facility Name
AZ Sint-Jan
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Hopital Universitaire Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
H. Hartziekenhuis - Roeselaere.
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Facility Name
Centre Hospitalier Peltzer-La Tourelle
City
Verviers
ZIP/Postal Code
B-4800
Country
Belgium
Facility Name
University Hospital - Olomouc
City
Olomouc
ZIP/Postal Code
775 20
Country
Czech Republic
Facility Name
Institute of Hematology and Blood Transfusion
City
Prague
ZIP/Postal Code
128 20
Country
Czech Republic
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Hotel Dieu de Paris
City
Paris
ZIP/Postal Code
75181
Country
France
Facility Name
Ruprecht - Karls - Universitaet Heidelberg
City
Heidelberg
ZIP/Postal Code
D-69117
Country
Germany
Facility Name
Marienhospital Stuttgart
City
Stuttgart
ZIP/Postal Code
70199
Country
Germany
Facility Name
Southwest German Cancer Center at Eberhard-Karls-University
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Ospedale San Salvatore
City
Pesaro
ZIP/Postal Code
I-61100
Country
Italy
Facility Name
Vrije Universiteit Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1007 MB
Country
Netherlands
Facility Name
Ziekenhuis Bronovo
City
Den Haag
ZIP/Postal Code
2597AX
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Universitair Medisch Centrum St. Radboud - Nijmegen
City
Nijmegen
ZIP/Postal Code
NL-6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
22102701
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result

Learn more about this trial

Infliximab in Treating Patients With Myelodysplastic Syndrome

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