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	Closed	18 and over		FHCRC-760.1 NCI-V94-0403

Objectives

I.  Assess the safety and toxicity of repetitive daily doses of interleukin-6 
(IL-6) administered with granulocyte-macrophage colony stimulating factor 
(GM-CSF) prior to and following myelosuppressive chemotherapy and autologous 
bone marrow transplantation in patients with nonhematologic malignancies.

II.  Identify a safe and effective biologic dose and/or maximum tolerated dose 
of IL-6 for future clinical testing.

III.  Evaluate the rate of hematopoietic recovery after myelosuppressive 
chemotherapy and the influence of IL-6 on attenuation of thrombocytopenia or 
acceleration of platelet count recovery.

IV.  Assess any change in the safety, tolerance, or treatment-limiting 
toxicities of IL-6 given in combination with GM-CSF.

Entry Criteria

Disease Characteristics:

Biopsy-proven nonhematologic tumor with histologic or clinical evidence of
advanced disease

The following tumor types are eligible:
  Stage II/III breast cancer with 10 or more positive nodes
  Stage IV breast cancer that is hormone refractory, with or without prior
     chemotherapy
  Stage II/III ovarian cancer with at least 1 prior course of platinum-based
     therapy
  Limited or extensive stage small cell lung cancer
  Germ cell tumors that failed first-line therapy
  Dukes' Stage C/D or recurrent colon cancer
  Pancreatic cancer of any stage
  Incompletely resected gastric or esophageal cancer

No history of any of the following:
  Kaposi's Sarcoma
  Multiple myeloma/monoclonal gammopathy
  B- or T-cell neoplasm

Eligible for autologous bone marrow transplantation at a participating
institution
  At least 1.5 x 10 to the eighth total noncleaved cells/kg harvested
  Marrow free of tumor
     Breast cancer patients may have marrow that is positive on
     immunocytochemistry only

Any CNS metastases must have been excised or irradiated at least 3 months
previously and patient must be clinically stable with no history of seizures

Pretreatment marrow cellularity adequate

Hormone receptor status:
  Not specified

Prior/Concurrent Therapy:

See Disease Characteristics

No prior interleukin-6

No plans to purge bone marrow either chemically or with monoclonal antibodies

Patient Characteristics:

Age:
  18 and over

Performance status:
   Able to meet institutional eligibility requirements

Hematopoietic:
  AGC at least 1,500
  Platelets at least 150,000 but no more than 500,000
  Hb at least 10.0 g/dl (may transfuse)

Hepatic:
  Bilirubin no more than 1.5 mg/dl
  SGOT and SGPT no more than 2.0 x ULN
  PT and PTT no more than 1.5 x control

Renal:
  Creatinine no more than 2.0 mg/dl
  Proteinuria and hematuria no more than 1+

Other:
  Able to meet institutional cardiac and pulmonary function requirements for
     autologous bone marrow transplantation
  No history of allergy to gentamicin or gentamicin analogues
  HIV and hepatitis B seronegative
  No autoimmune disease (e.g., severe rheumatoid arthritis, widespread active
     psoriasis)
  No pregnant or nursing women
  Adequate contraception required of sexually active, fertile women

Expected Enrollment

Up to 26 patients will be enrolled.

Outline

Randomized study.  All patients are treated on Regimen A.  Following a 
preparative regimen (high-dose chemotherapy with or without radiotherapy) and 
autologous bone marrow transplantation (ABMT), patients are randomized 3:1 to 
Arms I and II.

Regimen A:  Hematopoietic Stimulation.  Interleukin-6 (Serono), IL-6, 
NSC-658932; Granulocyte-Macrophage Colony Stimulating Factor Therapy 
(Immunex), GM-CSF, NSC-613795.

Arm I:  Hematopoietic Stimulation.  IL-6; GM-CSF.

Arm II:  Hematopoietic Stimulation.  GM-CSF.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

William Bensinger, MD, Protocol chair		Ph: 206-667-4933