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.

Condition	Treatment or Intervention	Phase
Previously Treated Myelodysplastic Syndrome secondary myelodysplastic syndrome de novo myelodysplastic syndrome refractory anemia with excess blasts in transformation refractory anemia with excess blasts	Drug: monoclonal antibody HuG1-M195	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

Austria
      Innsbruck Universitaetsklinik, Innsbruck,  A-6020,  Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria
Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      Ludwig Institute for Cancer Research-Brussels Branch, Brussels,  B-1200,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Denmark
      Herlev Hospital - University Hospital of Copenhagen, Herlev,  DK-2730,  Denmark
France
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France
      Centre Leon Berard, Lyon,  69373,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
      Institut Claudius Regaud, Toulouse,  31052,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Klinikum Nurnberg, Nuremberg (Nurnberg),  D-90419,  Germany
      Universitaetsklinik und Strahlenklinik - Essen, ESSEN,  D-45122,  Germany
Netherlands
      Academisch Ziekenhuis der Vrije Universiteit, Amsterdam,  1117 MB,  Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands
      Antoni van Leeuwenhoekhuis, Amsterdam,  1066 CX,  Netherlands
      Rotterdam Cancer Institute, Rotterdam,  3075 EA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6252 HB,  Netherlands
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway
Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonsspital - Saint Gallen, Saint Gallen,  CH-9007,  Switzerland
      University Hospital, Basel,  CH-4031,  Switzerland
United Kingdom, England
      Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
United Kingdom, Scotland
      C.R.C. Beatson Laboratories, Glasgow,  Scotland,  G61 1BD,  United Kingdom
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom
      Western General Hospital, Edinburgh,  Scotland,  EH4 9NQ,  United Kingdom

Study chairs or principal investigators

Heinz Zwierzina,  Study Chair,  EORTC Biological Therapeutics Development Study Group   

Study ID Numbers:  CDR0000067188; EORTC-13981
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003984
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08