Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	RPMI-DS-9429 NCI-T94-0072D, T94-0072

Objectives

I.  Assess the maximum tolerated dose of interleukin-6 (IL-6) given in 
combination with granulocyte-macrophage colony stimulating factor (GM-CSF) and 
erythropoietin (EPO) in patients with myelodysplastic syndrome.

II.  Evaluate the hematopoietic efficacy of GM-CSF/IL-6/EPO in this patient 
population.

III.  Evaluate the need for a GM-CSF priming phase for erythroid and platelet 
response.

IV.  Correlate in vivo effects with laboratory analysis of clonality and 
immunophenotype.

Entry Criteria

Disease Characteristics:

Myelodysplastic syndrome of 1 of the following FAB
classifications:
  Refractory anemia (RA)
  RA with ringed sideroblasts (RARS)
  RA with excess blasts (RAEB)
  RA with excess blasts in transformation (RAEBT)

De novo and secondary myelodysplastic syndromes eligible

No acute myeloid or chronic myelomonocytic leukemia

No history of any of the following:
  Kaposi's sarcoma
  Multiple myeloma
  Monoclonal gammopathy
  B- or T-cell neoplasm

At least 1 of the following hematologic parameters must be met:
  ANC no greater than 1,000
  Platelets 20,000-50,000 and not refractory to platelet
     transfusion
  Transfusion-dependent anemia OR
  Hb less than 10 g/dl

Prior/Concurrent Therapy:

Biologic therapy:
  No prior interleukin-6
  At least 2 weeks since growth factor therapy

Chemotherapy:
  At least 4 weeks since chemotherapy

Endocrine therapy:
  No requirement for steroids except as replacement therapy
  At least 2 weeks since danazol or other steroid therapy

Radiotherapy:
  Not specified

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 70-100%

Life expectancy:
  At least 3 months

Hematopoietic:
  See Disease Characteristics

Hepatic:
  Bilirubin no greater than 1.5 x ULN
  SGPT no greater than 1.5 x ULN
  PT and PTT no greater than 1.5 x ULN

Renal:
  Creatinine no greater than 2.0 mg/dl

Cardiovascular:
  No CHF
  No active coronary artery disease
  No history of cardiac arrhythmia
  No history of thrombotic events (except superficial
     thrombophlebitis)

Other:
  No prior hypersensitivity to growth factors
  No allergy to gentamicin
  No uncorrected iron deficiency, i.e.:
     Absence of marrow stores by Prussian blue stain 
     Iron saturation 15% or less
     Ferritin 20 mg/liter or less
  No autoimmune disorder
  No evidence of HIV infection (testing not required)
  No active hepatitis (screening required)
  No life-threatening or uncontrolled infection
  No other serious medical or psychiatric illness
  No surgical or medical condition that would preclude protocol
     therapy
  No second active malignancy except nonmelanomatous skin
     cancer
  No pregnant women
  Adequate birth control required of fertile women

Liver function tests, iron studies, creatinine and hepatitis
screen and bone marrow aspirate and biopsy to determine
eligibility completed within 14 days prior to registration;
other blood/body fluid analyses to determine eligibility
completed within 2 days prior to registration

Expected Enrollment

18 to 24 patients will be accrued.

Outline

The following acronyms are used:
  EPO        Epoetin alfa, NSC-628281
  GM-CSF     Granulocyte-Macrophage Colony Stimulating Factor
             (Hoechst/Immunex), NSC-613795
  IL-6       Interleukin-6 (Serono), NSC-658932

Growth Factor Therapy.  GM-CSF; EPO; IL-6.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Steven Bernstein, MD, Protocol chair(Contact information may not be current)		Ph: 877-275-7724; 800-685-6825