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

Alternate Title

Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 to 60	NCI	MDA-DM-94028 NCI-T95-0064D, T95-0064

Objectives

I.  Evaluate the feasibility of introducing MDR-1 cDNA into normal 
hematopoietic early progenitor cells by transduction with a safety-modified 
virus that bears the MDR-1 cDNA transcriptional unit.

II.  Assess the effects of MDR-modified stem cells on hematopoietic function 
during and after transplant in advanced breast cancer patients treated with 
MDR-transduced stem cells.
 

Entry Criteria

Disease Characteristics:

Stage III/IV breast cancer that has failed conventional-dose therapy or
induction therapy including platinum analogues

Measurable or evaluable lesion

No evidence of bone marrow involvement

Hormone receptor status:
  Not specified

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  See Disease Characteristics
  No prior paclitaxel
  No prior carboplatin-induced toxicity that required a 2-week treatment delay
     at doses of less than 300 mg per square meter

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior irradiation of more than 20% of bone marrow

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 to 60

Sex:
  Not specified

Menopausal status:
  Any status

Performance status:
  Zubrod 0 or 1

Hematopoietic:
  ANC at least 1,800
  Platelets at least 100,000
  Hemoglobin at least 8 g/dL
  Not refractory to platelet infusions (or at least 8 collections of
     autologous platelets available)

Hepatic:
  Bilirubin less than 2 mg/dL
  AST normal

Renal:
  Creatinine less than 1.6 mg/dL
  Creatinine clearance normal

Cardiovascular:
  Left ventricular ejection fraction at least 50% by MUGA
  No prior congestive heart failure
  No prior coronary artery disease
  No NYHA class III/IV status

Pulmonary:
  FEV1/DLCO greater than 50% of predicted

Other:
  No infection
  No history of bowel obstruction
  No history of grade II-IV neuropathy
  No pregnant or nursing women
  Adequate contraception required of fertile women

Expected Enrollment

15-20 patients will be entered over 1-2 years to provide 10 evaluable 
patients.  The study will close if there is an unacceptable incidence of 
mortality, 3 consecutive patients fail to engraft, or hematopoietic recovery 
is delayed.

Outline

Following hematopoietic stimulation with etoposide, cyclophosphamide, and 
G-CSF, peripheral blood stem cells are collected.  The cells are positively 
selected for those with the CD34 antigen.  The CD34+ cells are then transduced 
with a safety-modified retrovirus that carries the multidrug resistance-1 cDNA 
transcription unit.

Upon recovery from stem cell collection, patients are treated with high-dose 
carmustine, thiotepa, and cyclophosphamide for 3 days, followed by 
hematopoietic rescue with genetically modified peripheral blood stem cells.

Patients with no residual disease after transplantation are treated with 
paclitaxel and G-CSF every 3-4 weeks until disease progression or for a 
maximum of 12 courses.  If the treatment is well tolerated, the paclitaxel 
dose is increased until moderate toxicity is encountered.

Patients are followed every 3 weeks for 6 months, every 3 months for 1.5 
years, then every 6 months for 3.5 years.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Richard Champlin, MD, Protocol chair		Ph: 713-792-3618; 800-392-1611 Email: rchampli@mdanderson.org