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AzTrials

Breast CancerPhase 2NCT01375023

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

A Phase 2 study testing Radiotherapy and Anti-Thymocyte Globulin in people with Breast Cancer, run by European Institute of Oncology at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Breast Cancer
What is being tested?
Radiotherapy and Anti-Thymocyte Globulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteItaly
Study dates
Jun 2009to Dec 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • European Institute of Oncology

    Milan, 20141

Other trials in Italy

About this study

Official title: 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

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.

Read the detailed description

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 transplantation.

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.

Conditions
Breast Cancer
Being tested
Radiotherapy, Anti-Thymocyte Globulin
Keywords
Allogenic Haematopoietic Cell Transplantation, Total Lymphoid Irradiation, Anti-Thymocyte Globulin, Triple Negative Breast Cancer
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiotherapyRadiation

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

  • Anti-Thymocyte GlobulinBiological

    Also called Thymoglobuline

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

Study groups in NCT01375023
Study groupRoleWhat they receive
Anti-Thymocyte Globulin+radiotherapyExperimentaltriple negative breast cancer patients treated with radiation and Anti-Thymocyte Globulin iv
Receives: Radiation: Radiotherapy; Biological: Anti-Thymocyte Globulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response to treatment according to RECIST criteria

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

    Measured: 90 after the baseline

Secondary outcomes (1)

  1. graft versus host disease (GVHD)

    incidence and severity of GVHD after one year from baseline

    Measured: Time Frame: Day +365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2011 (estimated)
  2. Study startJun 2009
  3. Primary completionJul 2013
  4. Study completionDec 2013

Why it stopped: Very low accrual rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01375023
Sponsor's protocol ID
IEO S438/508
Other IDs
2008-006262-28, 2008
Status last verified
Sep 2012
First submitted
15 Jun 2011
Last updated
22 Jun 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 11722994

  • 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.

    PubMed 9508181

  • 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.

    PubMed 17222778

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiotherapy and Anti-Thymocyte Globulin in people with Breast Cancer, run by European Institute of Oncology at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Very low accrual rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response to treatment according to RECIST criteria (time frame: 90 after the baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01375023, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2015.

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