Clinical trial NCT00003984: Monoclonal Antibody Therapy in Treating Patients With Primary Myelodysplastic Syndrome
Official title: Phase II Trial With a Recombinant Humanized Anti-CD33 Monoclonal Antibody (HuM195) in Patients With High Risk Primary Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-05-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have primary myelodysplastic syndrome.

Detailed description: OBJECTIVES: I. Assess the therapeutic activity of monoclonal antibody HuG1-M195 on peripheral blood and bone marrow blast cell count, blood leukocyte, reticulocyte, and platelet counts, and hemoglobin levels in patients with myelodysplastic syndrome with refractory anemia with excess blasts (RAEB) (greater than 10% bone marrow myeloblasts) or RAEB in transformation. II. Assess the efficacy of this drug in terms of duration of response in these patients. III. Evaluate the toxicity of this drug in these patients.

OUTLINE: Patients receive monoclonal antibody HuG1-M195 IV over 4 hours on days 1-4. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease after 2 courses are removed from study. Patients with stable disease receive no further treatment after 4 courses. Patients with complete or partial response receive treatment for 4 additional courses. Patients are followed at 11 and 39 days after end of course 4, monthly for 4 months, then every 3 months thereafter for 1 year from study entry.

PROJECTED ACCRUAL: A total of 14-25 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed primary myelodysplastic syndrome (MDS) with greater than 10% bone marrow blasts Refractory anemia with excess blasts (RAEB) OR RAEB in transformation No chronic myelomonocytic leukemia No secondary MDS after prior chemotherapy except if treatment was for acute myeloid leukemia No allogeneic bone marrow transplantation planned

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: At least 3 months Hematopoietic: Hemoglobin no greater than 10 g/dL OR transfusion requirement of at least 3 packs of RBCs per month OR Platelet count less than 50,000/mm3 OR Absolute neutrophil count less than 1,000/mm3 No disseminated intravascular coagulation defined as fibrinogen less than 100 mg/dL AND prolonged PT, PTT, or thrombin time AND platelet count less than 25,000/mm3 without transfusion Hepatic: Bilirubin no greater than 2.0 mg/dL Alkaline phosphatase no greater than 4 times upper limit of normal (ULN) (unless due to underlying disease or Gilbert's syndrome) SGPT and SGOT no greater than 4 times ULN (unless due to underlying disease or Gilbert's syndrome) Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension No congestive heart failure, cardiac arrhythmia, or angina pectoris No history of myocardial infarction within the past 6 months No other significant cardiovascular disease LVEF within normal range by MUGA or echocardiogram No active ischemia Pulmonary: No pulmonary dysfunction Other: No central or peripheral neuropathy No uncontrolled or unstable diabetes No other significant organ system dysfunction HIV negative No prior malignancy except basal cell carcinoma or carcinoma in situ of the uterus No active, uncontrolled infection Not pregnant or nursing Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 2 months since prior biologic therapy (e.g., hematopoietic growth factors or biological response modifiers) Chemotherapy: See Disease Characteristics At least 2 months since prior chemotherapy Endocrine therapy: At least 2 months since prior endocrine therapy Radiotherapy: At least 2 months since prior radiotherapy Concurrent radiotherapy allowed Surgery: At least 2 months since prior surgery Other: No other concurrent investigational drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Vienna
country: Austria
facility: Kaiser Franz Josef Hospital
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Ludwig Institute for Cancer Research-Brussels Branch
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Herlev
country: Denmark
facility: Herlev Hospital - University Hospital of Copenhagen
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lyon
country: France
facility: Centre Leon Berard
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Essen
country: Germany
facility: Universitaetsklinik und Strahlenklinik - Essen
city: Nuremberg (Nurnberg)
country: Germany
facility: Klinikum Nurnberg
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekhuis
city: Amsterdam
country: Netherlands
facility: Academisch Ziekenhuis der Vrije Universiteit
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Rotterdam Cancer Institute
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Basel
country: Switzerland
facility: University Hospital
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Saint Gallen
country: Switzerland
facility: Kantonsspital - Saint Gallen
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: C.R.C. Beatson Laboratories
state: Scotland
Study officials:
affiliation: Medical University Innsbruck
name: Heinz Zwierzina, MD
role: STUDY_CHAIR
References: