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Allogenic Haematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Refractory "Triple Negative" Breast Cancer

Phase 2
18 Years
70 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Allogenic Haematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Refractory "Triple Negative" Breast Cancer

Breast cancer (BC) is the most common cancer among women and approximately 45% of breast
cancer patients develop metastatic disease that generally remains incurable with a median
survival of approximately 18 to 24 months. A subpopulation emerging as having particularly
poor prognosis is patients who have disease that is receptor negative for oestrogen,
progestin and HER2/neu (triple receptor negative). Since no effective therapy is available
in this setting of patients, the investigators propose allogeneic haematopoietic cell

Recent advances in allogeneic haematopoietic cell transplantation (HCT) have led to reduced
intensity preparative regimens that are non-myeloablative and permit the development of
sustained donor chimerism. As a result, regimen related organ toxicities (RROT), and
consequently non-relapse mortality has been reduced. However, the incidence of acute and
chronic graft-versus-host disease (aGVHD and cGVHD, respectively) has remained a major
complication. Pre-clinical data, developed by the Stanford group, established that
nonmyeloablative conditioning with total lymphoid irradiation (TLI) combined with depletive
anti-T cell antibodies protects against GVHD by skewing peripheral T cell subsets to favour
suppressive regulatory T cells. The current proposal is a Phase II study evaluating safety
and activity of the allogeneic peripheral blood progenitor cell (PBPC) transplantation using
TLI/ATG conditioning regimen, the kinetics of donor haematopoietic cell engraftment and
chimerism, the incidence and severity of acute GVHD following allogeneic transplantation
using the novel preparative regimen of TLI combined with antithymocyte globulin (ATG).
Patients with triple negative breast cancer will be considered for transplantation using
donor grafts from HLA-matched related donors. The preparative regimen of TLI combined with
ATG is expected to result in high levels of sustained donor haematopoietic cell engraftment
with a significantly reduced incidence of acute GVHD.

Inclusion Criteria:

- Histologically or cytologically proven diagnosis of breast cancer with evidence of
unresectable, locally recurrent, or metastatic disease. Locally recurrent disease
must not be amenable to resection or radiation therapy with curative intent.

- Documentation of estrogen and progestin receptor (ER/PR) negative status and HER2/neu
receptor negative status (ie, FISH or CISH (where approved) negative or
immunohistochemistry 0 or +1).

- Prior treatment with an anthracycline, a taxane and alkylating agents alone or in
combination in the neoadjuvant, adjuvant or metastatic disease setting.

- Prior treatment with chemotherapy as follows: Receipt of adjuvant chemotherapy with
RECIST (appendix B) defined disease progression documented during treatment or
disease relapse within 6 months of last treatment, OR Receipt of chemotherapy in the
first-line advanced disease setting with RECIST defined disease stable or progression
documented during treatment, or, if the patient completed treatment with objective
disease response, documented disease progression after discontinuing treatment.
Patients entering the study on the basis of this criterion may have also previously
received neo adjuvant or adjuvant treatment with chemotherapy.

- Measurable disease as per RECIST. Measurable lesions that have been previously
radiated will not be considered target lesions unless increase in size has been
observed following completion of radiation therapy.

- Male or female.

- Patients age > 18 and < 70 years.

- ECOG performance status 0-2.

- Resolution of all acute toxic effects of prior therapy or surgical procedures to
grade ≤1 (except alopecia).

- Life expectancy >6 months.

- A fully HLA-identical sibling donor is available. Patients with one antigen
mismatched donors can be considered but only after discussion with the transplant
team and the Principal Investigator.

- The definitions of minimum adequacy for organ function required prior to study entry
are as follows: serum aspartate transaminase (AST) and serum alanine transaminase
(ALT) ≤2.5 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function
abnormalities are due to underlying malignancy; total serum bilirubin ≤1.5 x ULN;
serum albumin ≥3.0 g/dL; absolute neutrophil count (ANC) ≥1500/μL; platelets
≥100,000/μL; haemoglobin ≥9.0 g/dL; serum creatinine ≤1.5 x ULN

- Signed and dated informed consent

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.

Exclusion Criteria:

- Uncontrolled CNS involvement with disease

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Females who are pregnant

- Organ dysfunction defined as follows: cardiac ejection fraction <30% or uncontrolled
cardiac failure; pulmonary: DLCO <40% predicted; liver: elevation of bilirubin to >
1.5 X ULN and/or transaminases >5x the upper limit of normal Renal: Serum creatinine
>1.5 x ULN

- ECOG performance status > 2

- Patients with poorly controlled hypertension on multiple antihypertensives

- Documented fungal disease that is progressive despite treatment

- Viral infections: HIV positive patients. Hepatitis B and C positive patients will be
evaluated on a case by case basis

- Psychiatric disorders or psychosocial problems which in the opinion of the primary
physician or Principal Investigator would place the patient at unacceptable risk from
this regimen.

- Patients may not be receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to agents used in the study.

- Any previous or current malignancy at other sites, with the exception of adequately
treated cone-biopsied in situ carcinoma of the cervix and adequately treated basal or
squamous cell carcinoma of the skin.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response to treatment according to RECIST criteria

Outcome Description:

Response to treatment according to RECIST criteria evaluated after 90 days from baseline

Outcome Time Frame:

90 after the baseline

Safety Issue:


Principal Investigator

Rocco Pastano, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

European Institute of Oncology


Italy: Ethics Committee

Study ID:

IEO S438/508



Start Date:

June 2009

Completion Date:

December 2013

Related Keywords:

  • Breast Cancer
  • Allogenic Haematopoietic Cell Transplantation
  • Total Lymphoid Irradiation
  • Anti-Thymocyte Globulin
  • Triple Negative Breast Cancer
  • Breast Neoplasms