Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Breast Neoplasms

Neoplasm Metastasis

Inflammatory Breast Neoplasms

Neoplastic Processes

Breast Diseases

Skin Diseases

Inflammatory Breast Cancer

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Etoposide

Cyclophosphamide

Melphalan

Etoposide phosphate

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Monoclonal Antibody 3A1

Monoclonal Antibody 95-5-49

Monoclonal Antibody 95-6-22

Baxter Isolex 3001 Stem Cell Selection System

Ceprate SC

Ronald E Gress, M.D.

This study will evaluate the effectiveness of combination chemotherapy with paclitaxel (Taxol) and cyclophosphamide (Cytoxan), followed by high-dose melphalan and etoposide for treating inflammatory breast cancer. Patients also receive infusions of their own previously collected progenitor cells (primitive cells that can make new cells to replace ones destroyed by chemotherapy).

Patients 18 years of age or older with stage IIIB inflammatory breast cancer that has not metastasized (spread beyond the breast) may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and chest x-ray. They have computed tomography (CT) of the head, chest, abdomen and pelvis as well as a bone scan to determine the extent of disease, and a nuclear medicine scan called MUGA to examine the heart's pumping ability. They may receive a rehabilitation medicine evaluation.

Participants undergo the following tests and procedures:

* Central venous line placement: Patients have a central venous line (plastic tube) placed into a major vein in the chest before beginning treatment. The line remains in the body throughout treatment and is used to give chemotherapy and other medications and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room.
* Chemotherapy: Patients receive two or more cycles of paclitaxel and cyclophosphamide. Paclitaxel is given intravenously (I.V., through a vein) for 72 hours using a portable pump. Cyclophosphamide is given daily for 3 days I.V. over 1 hour. The cycles may be 28 days apart. A drug called Mesna is given with this treatment to protect the bladder from irritation from cyclophosphamide. Patients who have not previously been treated with doxorubicin (Adriamycin) may receive a maximum of four cycles of doxorubicin and cyclophosphamide by vein on a single day during each cycle, with cycles 21 days apart. When all the paclitaxel/cyclophosphamide cycles are completed, patients receive melphalan and etoposide, both drugs I.V. over 1 to 8 hours for three consecutive days.
* G-CSF treatment: After each paclitaxel/cyclophosphamide cycle and after the melphalan/etoposide treatment, patients are given a drug called G-CSF. G-CSF, injected under the skin, stimulates production of infection-fighting white blood cells.
* Apheresis: This is a procedure to collect progenitor cells for later reinfusion. For this procedure, blood is collected through a catheter (plastic tube) placed in an arm vein. The blood is circulated through a cell-separating machine, where the white cells, including the progenitor cells, are extracted, and the red cells are returned to the patient through another catheter in the other arm. Apheresis is done after each of two cycles of paclitaxel/cyclophosphamide.
* Progenitor cell transplant: Progenitor cells are reinfused after melphalan/etoposide treatment.
* Glucose infusion: A salt solution with chemically modified glucose is infused I.V. over a period of from 12 to 48 hours, with subsequent donation of blood cells for blood and immune system studies. Patients have a maximum of two glucose infusions, separated by at least 3 months.
* Tumor biopsy: Some patients have a biopsy of their tumor (removal of a small piece of tumor tissue for microscopic study) before starting chemotherapy.
* Blood tests: Blood is drawn frequently to monitor safety and treatment response, and for research purposes.
* Dental consultation: Some patients may have a dental consultation before the progenitor cell transplant.

BACKGROUND:

Efforts to cure high-risk breast cancer have increasingly focused on the application of dose intensive chemotherapy. To date, the use of dose intensive and high-dose chemotherapy has not significantly changed the survival for the majority of high risk and metastatic patients. The optimal schedule and combination of agents to improve the results of high-dose chemotherapy is not known. This study will pilot a combination of chemotherapy agents for the treatment of Inflammatory Breast Cancer.

OBJECTIVES:

To define, in a statistically relevant manner, the clinical efficacy of this chemotherapy regimen combination in the treatment of Inflammatory Breast Cancer (stage IIIB inflammatory).

To examine the effects of this high-dose chemotherapy on T-cells (T-cell number, phenotype, cytokine profiles) and study the process of post-chemotherapy T-cell regeneration.

ELIGIBILITY:

Newly diagnosed patient with non metastatic Inflammatory Breast Cancer (stage III B).

The patients treated in this study will also be eligible for entrance into other protocols of the experimental Transplantation \& Immunology Branch that are examining strategies of manipulating T-cell regeneration in adults after intensive chemotherapy.

DESIGN:

Patients will receive multiple cycles of a dose intensive combination of Paclitaxel and Cyclophosphamide both for the mobilization of peripheral blood progenitor cells and with therapeutic intent. A second induction regimen will consist of four cycles of the combination of Doxorubicin / cyclophosphamide. Patients will subsequently receive high-dose Melphalan and Etoposide followed by the infusion of peripheral blood progenitor cells and granulocytes colony-stimulating-factor (G-CSF).

Chemotherapy and Progenitor Cell Transplantation to Treat Inflammatory Breast Cancer

A Multi-Center Study of Paclitaxel/Cyclophosphamide and High Dose Melphalan/Etoposide With Autologous Progenitor Cell Transplantation for the Treatment of Inflammatory Breast Cancer

National Cancer Institute (NCI)

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Cytarabine

Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.

* Intermediate dose during induction phase to remission.
* High-dose during consolidation phase in patients with favorable cytogenetics.

Ara-C

* In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission.
* In patients with other cytogenetics without HLA-Identical sibling.

Autologous transplantation

* Patients without favorable or normal karyotype(and one course to CR).
* Patients with normal karyotype who need two cycles of chemotherapy to achieve CR, and other cytogenetics.

Allogeneic HLA-identical sibling transplantation

In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.

CD34+ selection

Jorge Sierra, MD

Salut Brunet, MD

In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years, the Spanish CETLAM group showed a complete remission rate 75 % using the combination of daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3 days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during induction and risk-adapted post remission treatment based on the improvement in prognostic characterization of AML and the implementation of novel transplantation techniques.

Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.

Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).

Risk-stratification according to cytogenetics, courses to CR and availability of an HLA-identical sibling:

* Patients in the favorable cytogenetics group \[t(8;21), inv(16) or t(16;16)\] are treated with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).
* Patients in intermediate cytogenetics group (normal karyotype and a single course to achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant, regardless of having an HLA-identical sibling.
* The remaining patients are considered in the high-risk group and are treated with autologous or allogeneic PBSC transplantation depending on the availability of a sibling donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.

Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.

Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.

Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.

Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.

CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.

Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Chemotherapy and Progenitor Cell Transplantation to Treat Inflammatory Breast Cancer	NCT00001507	Breast Neoplasm Neoplasm Metast...	Monoclonal Anti... Monoclonal Anti... Monoclonal Anti... Baxter Isolex 3... Ceprate SC	18 Years -	National Institutes of Health Clinical Center (CC)
Risk-adapted Therapy for Adult Acute Myeloid Leukemia.	NCT01716793	Leukemia, Myelo...	Ara-C Autologous tran... Allogeneic HLA-... CD34+ selection	18 Years - 60 Years	Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Spots Global Cancer Trial Database for cd34+ selection