Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information

Alternate Title

Combination Chemotherapy Followed By Bone Marrow Transplantation in Treating Patients With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 to 60	NCI	NCI-92-C-0161I NCI-MB-294, NCI-T92-0018N, T92-0018

Objectives

I.  Study the feasibility of obtaining bone marrow engraftment with 
retrovirally transduced hematopoietic stem cells bearing neomycin-resistance 
marker genes (neo-r) following high-dose chemotherapy with 
ifosfamide/carboplatin/etoposide (ICE) in patients with metastatic breast 
cancer.

II.  Study the distribution and survival times of neo-r-transduced bone marrow 
cells and peripheral blood stem cells in the peripheral blood and bone marrow 
during bone marrow engraftment following high-dose chemotherapy.

III.  Study the effects of chemotherapy on the neo-r-transduced stem cells and 
progeny following bone marrow engraftment.

IV.  Study the effects of hematopoietic growth factor administration on the 
neo-r-transduced bone marrow and peripheral blood cells.

V.  Improve retroviral transduction efficiency into true repopulating stem 
cells in order to achieve the above objectives.

VI.  Compare in the same patient population three transduction techniques:  
retroviral supernatant with hematopoietic growth factors, without 
hematopoietic growth factors, or with stromal cells.

Entry Criteria

Disease Characteristics:

Histologically documented metastatic breast cancer that has achieved at least
a partial response to induction chemotherapy on an NCI Medicine Branch (MB)
protocol that includes G-CSF
  Patients who are Stage IV with no evidence of disease following induction
     eligible
  Patients ineligible for other NCI-MB protocols receive induction on this
     protocol

No history or clinical evidence of CNS metastases

No evidence of metastatic disease to the pelvis on plain film or bone scan

No more than 3 sites of metastatic disease on bone scan

Histologically negative bilateral bone marrow biopsy required prior to harvest

Hormone receptor status:
  Not specified

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No more than 1 prior chemotherapy regimen for metastatic disease allowed
  Induction chemotherapy at the Medicine Branch or on this protocol required

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior pelvic radiotherapy

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 to 60

Sex:
  Women and men

Menopausal status:
  Not specified

Performance status:
  ECOG 0-2

Life expectancy:
  Greater than 60 days

Hematopoietic:
  Not specified

Hepatic:
  Bilirubin no greater than 1.5 mg/dL
  AST no greater than 2 times normal
  PT/PTT normal

Renal:
  Creatinine clearance at least 50 mL/min
  Calcium normal

Cardiovascular:
  Left ventricular ejection fraction greater than 40%
  No history of angina
  No history of myocardial infarction
  No history of congestive heart failure

Pulmonary:
  DLCO greater than 50% (compensated for hemoglobin)
  FEV greater than 55%
  pO2 greater than 60 mm Hg

Other:
  Marrow harvest greater than 0.5 x 10 to the eighth nucleated cells/kg body
     weight is required for transplantation
  HIV and HBsAg seronegative
  Good psychiatric and medical risk
  Negative pregnancy test required of fertile women

Expected Enrollment

A maximum of 18 patients will be entered at a rate of 6-8 patients/year.

Outline

All patients should receive induction on an NCI Medicine Branch protocol that 
includes granulocyte colony-stimulating factor (G-CSF); those not eligible for 
ongoing studies receive induction with fluorouracil, leucovorin, doxorubicin, 
and cyclophosphamide (FLAC) with G-CSF support every 21 days for a minimum of 
2 courses.

Responding patients undergo peripheral blood stem cell (PBSC) mobilization 
with cyclophosphamide and G-CSF followed by PBSC and bone marrow harvest.  If 
collections are adequate, some of the cells are retrovirally transfected in 
vitro with the neomycin-resistance marker genes G1N.40 and LNL6.

Patients then receive 4 days of high-dose therapy with ifosfamide, 
cyclophosphamide, and etoposide (ICE) followed on day 7 by autologous 
transplantation with the PBSC and bone marrow.

Patients with residual or progressive disease following treatment are offered 
salvage therapy with paclitaxel and G-CSF or, for those who have had prior 
paclitaxel for metastatic disease, with vinblastine and G-CSF.  Courses repeat 
every 21 days until disease is stable for 3 courses or until disease 
progression.

Dunbar CE, Cottler-Fox M, O'Shaughnessy JA, et al.: Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation. Blood 85 (11): 3048-57, 1995.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Kenneth Cowan, MD, PhD, Protocol chair		Ph: 402-559-4238 Email: kcowan@unmc.edu