Infliximab in Treating Patients With Myelodysplastic Syndrome

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00074074

Collaborator

(none)

Enrollment

Locations

2.4

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Biological: infliximab	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Masking:

None (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

Study Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Dec 1, 2006

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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