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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	16-75		WPCI-9175 NCI-V91-0215

Objectives

I.  Evaluate the safety and tolerability of interleukin-6 (IL-6) administered 
subcutaneously to thrombocytopenic patients with myelodysplastic syndrome.

II.  Assess the hematopoietic and other pharmacologic effects of various 
dosages of IL-6.

III.  Obtain preliminary information on the pharmacodynamic and 
pharmacokinetic properties of IL-6 administered to this patient population.
 

Entry Criteria

Disease Characteristics:

Histologically confirmed myelodysplastic syndrome (MDS) defined
by the following FAB criteria:
  Refractory anemia
  Refractory anemia with ringed sideroblasts
  Chronic myelomonocytic leukemia

Thrombocytopenia due to MDS required
  Platelet count no greater than 100,000 on 3 successive
  evaluations within 2-4 weeks prior to entry

Less than 5% bone marrow blast cells required

No extensive myelofibrosis on bone marrow biopsy

No history of lymphoproliferative disease

Prior/Concurrent Therapy:

Biologic therapy:
  At least 4 weeks since immunosuppressive drugs
  At least 8 weeks since other cytokine or biological agent,
  e.g.:
      No G-CSF or GM-CSF
      No EPO
      No TNF
      No IL-2 or IL-3
      No interferon
   
Chemotherapy:
  At least 4 weeks since cytotoxic or maturational chemotherapy
  At least 6 months since chemotherapy-induced bone marrow
  failure

Endocrine therapy:
  At least 4 weeks since hormonal therapy

Radiotherapy:
  Not specified

Surgery:
  Not specified

Other:
  At least 4 weeks since treatment with investigational agents
  At least 4 weeks since other therapy for MDS
  At least 24 hours since NSAIDs or antipyretics
  No prior bone marrow transplant

Patient Characteristics:

Age:
  16-75

Performance status:
  Karnofsky greater than 60%

Hematopoietic:
  See Disease Characteristics

Hepatic:
  Bilirubin no more than 2.0 x ULN
  SGOT no more than 3.0 x ULN
  Alkaline phosphatase no more than 3.0 x ULN
  No history of clinically significant coagulation disorders,  
  i.e.:
      No prolonged PT or PTT
      No specific coagulation factor deficiencies
      No chronic or acute hepatitis of any etiology

Renal:
  Creatinine no more than 1.8 mg/dl
  BUN no more than 30 mg/dl
  No history of chronic glomerulopathy

Cardiovascular:
  No significant cardiovascular disease, i.e.:
    No clinical evidence of CHF
    No angina pectoris
    No myocardial infarction within 5 years of entry
    No arrhythmia requiring therapy
    No history of stroke

Other:
  No severe endocrine or metabolic disease, i.e.:
    No uncontrolled DM
    No hyperthyrodism or hypothyrodism
    No Cushings disease
  No metabolic bone disorders
  No HIV-positive patients
  No history of anaphylaxis or active allergic disorder (e.g.,
     asthma)
  No history of Kaposi's sarcoma
  No history of autoimmune disease or immunodeficiency disorder
  No history of endometriosis
  No active GI bleeding
  No malignancy within 2 years requiring therapy except:
    Nonmelanomatous skin cancer
    In situ cervical cancer
  No major neurologic or psychiatric disease, e.g.:
    No abnormal neurologic examination
    No seizure disorder
    No history of epilepsy
    No dementia or altered mental status that would preclude
        participation in study
  No active infection requiring systemic therapy
  Negative HCG test required of fertile women within 24 hours 
     of treatment
  No nursing women
  Adequate contraception required of fertile women:
    Medically approved method used for 30 days prior to entry  
    and continued for duration of study

Expected Enrollment

Approximately 28-42 patients will be collectively enrolled among 3 centers in 
dose escalation cohorts of 4-6 patients at each of the 7 planned dosage 
levels.  Study duration is approximately 50 days with option of up to 6 months 
maintenance therapy.

Outline

Nonrandomized study.

Biological Response Modifier Therapy.  Interleukin-6 (Sandoz), IL-6.

Trial Contact Information

Trial Lead Organizations

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

John Nemunaitis, MD, Protocol chair(Contact information may not be current)		Ph: 214-370-1822 Email: john.nemunaitis@USOncology.com