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 to 65		MSKCC-93060 NCI-V93-0270

Objectives

I.  Determine the ability of various doses of recombinant methionyl human stem 
cell factor (r-metHuSCF) given in combination with granulocyte colony 
stimulating factor (G-CSF) to mobilize peripheral blood progenitor cells 
(PBPC) in non-Hodgkin's lymphoma patients as measured by the numbers of 
circulating committed progenitors (CFU), circulating CD34 cells, and 
erythrocyte blood forming units (BFU-E).

II.  Assess the safety of r-metHuSCF administered in combination with G-CSF 
prior to marrow-ablative chemotherapy in these patients.

III.  Document the rate of hematopoietic recovery after transplantation of 
PBPC mobilized by r-metHuSCF and G-CSF in these patients.

Entry Criteria

Disease Characteristics:

Histologically or morphologically confirmed intermediate- or 
immunoblastic high-grade non-Hodgkin's lymphoma in second
remission or in chemosensitive first relapse
  Chemosensitive defined as having achieved at least a
  partial response to standard-dose chemotherapy within 3
  months prior to entry

No marrow involvement by tumor on bone marrow aspiration and
biopsy

No documented CNS involvement

Prior/Concurrent Therapy:

More than 4 weeks since enrollment on any other protocol using
investigational drugs

No concurrent investigational agents

Biologic therapy:
  At least 2 weeks since hematopoietic growth factor therapy,
     with recovery required
  No concomitant hematopoietic growth factor

Chemotherapy:
  At least 3 weeks since induction chemotherapy, with recovery
     required
  No concomitant systemic or intrathecal cytotoxic drugs

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy to 25% or more of bone marrow
  At least 3 weeks since radiotherapy, with recovery required
  No concomitant radiotherapy

Surgery:
  Not specified

Other: 
  No prior bone marrow transplant

Patient Characteristics:

Age:
  18-65

Performance status:
  Karnofsky 80-100%

Life expectancy:
  At least 6 months

Hematopoietic:
  ANC at least 1,500
  Platelets at least 100,000
  Hb at least 9.0 g/dl (may be transfused)

Hepatic:
  Bilirubin less than 2.0 mg/dl

Renal:
  Creatinine less than 2.0 mg/dl

Cardiovascular:
  LVEF normal
  No uncontrolled hypertension (diastolic greater than 115 mm
     Hg)
  No unstable angina
  No CHF greater than NYHA class II
  No MI within 6 months
  No coronary angioplasty within 6 months
  No uncontrolled atrial or ventricular arrhythmia
  No concurrent beta-adrenergic blocking agents

Pulmonary:
  FEV and FVC at least 60%

Other:
  No asthma within 3 years, including:
     Allergic asthma
     Asthma induced by cold, infection, or exercise
  No other significant IgE-mediated hypersensitivities,
  including but not limited to:
     Allergic rhinitis 
     Allergic eczema
     History of anaphylactic reactions
     Chronic or recurrent urticaria 
     Acquired or congenital angioedema
  No known allergy to E. coli-derived products
  At least 2 weeks since monoamine oxidase
     inhibitors
  No concurrent monoamine oxidase inhibitors
  No active infection or temperature of 38.2 C or greater
  No previously documented HIV infection
  No poorly controlled diabetes
  No other significant nonmalignant disease
  No psychiatric, addictive, or other disorder that might
     preclude informed consent
  No prior malignancy with 5 years except:
     Surgically cured basal cell carcinoma
     In situ carcinoma of the cervix
  No pregnant or nursing women

Expected Enrollment

A minimum of 6 patients/arm will be accrued over approximately 6 months; 2 
additional patients/institution will be accrued at the effective dose to a 
maximum of 30 patients.

Outline

Randomized study.  For the collection phase of the study, patients are 
initially randomized in a 1:2 ratio to Arms I and II, respectively, until Arm 
II is filled; patients are then randomized in a 1:2 ratio to Arms I and III.  
Following treatment on Arm I, II, or III, patients proceed to therapy on 
Regimen A.

Arm I:  Peripheral Blood Progenitor Cell (PBPC) Mobilization.  Granulocyte 
Colony Stimulating Factor (Amgen), G-CSF, NSC-614629.

Arm II:  PBPC Mobilization.  Recombinant Human Methionyl Stem Cell Factor, 
r-metHuSCF; SCF; G-CSF.  Low-dose r-metHuSCF.

Arm III:  PBPC Mobilization.  SCF; G-CSF.  Higher dose r-metHuSCF.

Regimen A:  3-Drug Combination Chemotherapy with Stem Cell Rescue and 
Hematopoietic Stimulation.  Cyclophosphamide, CTX, NSC-26271; Carmustine, 
BCNU, NSC-409962; Etoposide, VP-16, NSC-141540; with Peripheral Blood Stem 
Cells, PBSC; and G-CSF.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Janice Gabrilove, MD, Protocol chair		Ph: 212-241-9650 Email: janice.gabrilove@mssm.edu