Allogenic Haematopoietic Cell Transplantation for Patients With Refractory "Triple Negative" Breast Cancer

NCT01375023 | Terminated Phase 2

• 2 other identifiers: IEO S438/5082008-006262-28
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the engraftment, toxicity and anti-tumour activity of allogeneic peripheral blood progenitor cell (PBPC) transplantation using TLI/ATG conditioning regimen in patients with refractory "Triple Negative" breast cancer.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Response to treatment according to RECIST criteria

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

  90 after the baseline

Secondary Outcomes (1)

• graft versus host disease (GVHD)

  Time Frame: Day +365

Study Arms (1)

Anti-Thymocyte Globulin+radiotherapy

EXPERIMENTAL

triple negative breast cancer patients treated with radiation and Anti-Thymocyte Globulin iv

Radiation: Radiotherapy; Biological: Anti-Thymocyte Globulin

Interventions

Radiotherapy RADIATION

daily radiation therapy for 10 days, total dose of 80 cGY

Anti-Thymocyte Globulin+radiotherapy

Anti-Thymocyte Globulin BIOLOGICAL

1.5 mg/kg/day, IV from day -11 through day -7 before transplantation

Also known as: Thymoglobuline

Anti-Thymocyte Globulin+radiotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Institute of Oncology: lead
• Istituto Clinico Humanitas: collaborator

Study Sites (1)

European Institute of Oncology

Milan, 20141, Italy

Location

Related Publications (3)

• Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH. Non-myeloablative transplants for malignant disease. Hematology Am Soc Hematol Educ Program. 2001:375-91. doi: 10.1182/asheducation-2001.1.375.

  PMID: 11722994 BACKGROUND

• Ueno NT, Rondon G, Mirza NQ, Geisler DK, Anderlini P, Giralt SA, Andersson BS, Claxton DF, Gajewski JL, Khouri IF, Korbling M, Mehra RC, Przepiorka D, Rahman Z, Samuels BI, van Besien K, Hortobagyi GN, Champlin RE. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol. 1998 Mar;16(3):986-93. doi: 10.1200/JCO.1998.16.3.986.

  PMID: 9508181 BACKGROUND

• Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007 Jan;13(1 Suppl 1):87-97. doi: 10.1016/j.bbmt.2006.10.015.

  PMID: 17222778 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Radiotherapy; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Rocco Pastano, MD

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: June 17, 2011
• Study Start: June 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2013
• Last Updated: June 22, 2015

Record last verified: 2012-09

Locations

IT (1)