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	Completed	18 and over	NCI	BRMP-9102 NCI-91-C-113, NCI-T91-0020N, T91-0020

Objectives

I.  Determine whether an MTD for interleukin-3 (IL-3) exists within the 
intended dose range for this trial in patients with advanced cancer.
II.  Determine the MTD of cyclophosphamide (CTX) with IL-3 and 
granulocyte-macrophage colony stimulating factor (GM-CSF) support.
III.  Assess the toxicities of the proposed dose and schedule of IL-3/GM-CSF 
when given with CTX
IV.  Evaluate the pattern of IL-3/GM-CSF-modified nadirs and the period of 
recovery.
V.  Evaluate the ability of the cytokine regimen to maintain chemotherapy 
doses over several courses.
VI.  Obtain data regarding the numbers and cycle status of peripheral blood 
and bone marrow progenitors.

Entry Criteria

Disease Characteristics:

Histologically confirmed solid tumor or lymphoma considered
incurable by surgery, radiotherapy, or standard chemotherapy

Pathology must be reviewed at NIH
Tumor must be unresponsive to standard treatment regimens or
no effective therapy for malignancy exists

Enrollment priority given to cancers normally considered
cyclophosphamide-responsive:
  Lymphoma
  Breast cancer
  Lung cancer
  Ovarian cancer
  Genitourinary cancers

No overt tumor involvement of bone marrow (myelophthistic
cytopenia or leukoerythroblastic reaction) allowed

No history of CNS metastases

Measurable or evaluable disease required

Prior/Concurrent Therapy:

Biologic therapy:
  At least 4 weeks since prior immunotherapy

Chemotherapy:
  Prior cyclophosphamide allowed
  No prior nitrosoureas or mitomycin
  More than 2 cycles with other stem cell toxins (e.g.,
     melphalan, thiotepa, carboplatin) allowed at the
     discretion of the principal investigator
  At least 4 weeks since prior antineoplastic chemotherapy

Endocrine therapy:
  At least 4 weeks since prior hormonal therapy

Radiotherapy:
  No prior pelvic radiotherapy
  No prior radiotherapy to more than 20% of bone marrow
  At least 4 weeks since prior radiotherapy

Surgery:
  Not specified

Other:
  No concurrent requirement for the following medications:
     Steroids
     Anticoagulants
     Antiarrhythmics
     Antiepileptics
     Bronchodilators

Patient Characteristics:

Age:
  At least 18

Performance status:
  Karnofsky 70-100%

Life expectancy:
  At least 3 months

Hematopoietic:
  WBC at least 4,000
  ANC at least 1,500
  Platelets at least 100,000
  Hb at least 8 g/dl

Hepatic:
  Bilirubin less than 1.5 mg/dl (unless elevation
     ascribed to Gilbert's disease)
  SGOT less than 5 x normal
  Alkaline phosphatase less than 5 x normal
  PT less than 13 seconds
  PTT less than 35 seconds
  Albumin at least 3.0 mg/dl

Renal:
  Creatinine less than 1.5 mg/dl OR
  Creatinine clearance (calculated) greater than 50 ml/min
  Calcium less than 11.0 mg/dl

Cardiovascular:
  No history of CHF
  No history of arrhythmia requiring treatment

Other:
  No prior drug-induced hemorrhagic cystitis
  No history of adult asthma
  No known seizure disorder
  No evidence of HIV or hepatitis B infection
  No other active infectious process
  No bleeding disorders
  No other medical or psychiatric condition that would
     compromise patient's ability to tolerate treatment
  No nursing women
  Negative beta-HCG test required of premenopausal women
  Effective contraception required of fertile patients

Expected Enrollment

Approximately 30-48 patients will be studied.  With an anticipated annual 
accrual rate of 24 patients, it is expected that the study will be completed 
in 2 years.

Outline

Nonrandomized study.
Single-agent Chemotherapy with Urothelial Protection (as indicated) and Stem 
Cell Stimulation plus Hematologic Toxicity Attenuation.  Cyclophosphamide, 
CTX, NSC-26271; with (as indicated) Mesna, NSC-113891; and Interleukin-3 
(Sandoz), IL-3; Granulocyte-Macrophage Colony Stimulating Factor 
(Sandoz-Schering), GM-CSF, NSC-617589.

Trial Contact Information

Trial Lead Organizations

Clinical Research Branch

Langdon L. Miller, MD, Protocol chair		Ph: 616-833-9730; 800-253-8600 Email: langdon.l.miller@am.pnu.com