Stem Cell Transplant With Th2/Tc2 Cells to Treat Advanced Breast Cancer

NCT00079625 | Completed Phase 1

• 2 other identifiers: 04013104-C-0131
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1 trial will investigate the safety of a modified stem cell transplant procedure for treating advanced breast cancer. Patients with cancers can sometimes benefit greatly from transplants of stem cells (cells produced by the bone marrow that mature into blood cells). In addition to producing new bone marrow and restoring normal blood production and immunity, the donated cells fight any residual tumor cells that might have remained in the body, in what is called a "graft-versus-tumor" effect. However, severe problems, or sometimes even death, may follow these transplants as a result of the high-dose chemotherapy and radiation that accompany the procedure. Also, donated immune cells called lymphocytes, or T cells, sometimes attack healthy tissues in a reaction called graft-versus-host-disease (GVHD), damaging organs such as the liver, intestines and skin. This study will use the following strategies to try to reduce these risks:

• "Induction chemotherapy" to reduce patients' immunity in an attempt to prevent rejection of the donated stem cells
• Reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression
• Removal of lymphocytes from the donor stem cells for transfusion in small quantities at monthly intervals following the stem cell transplant to reduce the risk of GVHD
• Transplant of specific lymphocytes called Th2/Tc2 cells that may increase the percentage of donor stem cells accepted by the patient without significantly increasing GVHD Patients between 18 and 75 years of age with advanced (stage IV) breast cancer that does not respond to standard therapy may be eligible for this study. Candidates are screened with a medical history, physical and dental examinations, x-ray studies and bone marrow biopsies to evaluate disease status, blood and urine tests (including a blood test for genetic match with the donor), and lung and heart function tests. Participants have a central venous line (large plastic tube) placed into a major vein. This tube stays in the body during the entire treatment period for infusing the donated stem cells and T lymphocytes, giving medications, including chemotherapy and other drugs, antibiotics, and blood transfusions, and withdrawing blood samples. Treatment starts with induction chemotherapy, in which patients receive one or two cycles of the anti-cancer drugs fludarabine and cyclophosphamide. (One cycle consists of 4 days on drug therapy followed by a 17-day rest period.) G-CSF, a drug that boosts white cell production, is also given to reduce the risk of infection. Several days before the transplant procedure, patients begin conditioning chemotherapy with higher doses of cyclophosphamide and fludarabine. Three days after the conditioning therapy is completed, the stem cells are infused. To help prevent both rejection of the donor stem cells and GVHD, patients receive cyclosporine (first by vein and later by mouth) for several weeks after the transplant. Infusions of donor lymphocytes begin about 6 weeks after the transplant to boost the immune system and enhance the graft-versus-tumor effect. Patients may leave the hospital when they are able to eat and drink, have no fever or infection, and have a normal or near-normal white cell count. They return for follow-up visits twice a week for the first 100 days after the transplant, then every 3 months, then 6 months and then yearly for at least 5 years post-transplant. The visits include a medical history, physical examination, and blood draws, as well as disease staging with CT scans every month for the first 6 months.

Conditions

Breast Neoplasms

Keywords

Engraftment; Graft-Versus-Host Disease; Metastatic Breast Cancer; MBC

Outcome Measures

Primary Outcomes (1)

• To determine the safety as defined by the incidence of acute graft-versus-host disease and feasibility of administering in vitro generated donor T cells of Th2/Tc2 phenotype to augment a T cell depleted allograft after reduced-intensity conditio...

Secondary Outcomes (1)

• To determine if the transplantation of a T cell depleted allograft augmented with Th2/Tc2 ell can result in a state of rapid complete donor chimerism after reduced-intensity conditioning regimen.

Interventions

Th2/Tc2 Cells DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with measurable stage IV breast cancer. Patients with central nervous system CNS metastases are eligible if the CNS metastases have been treated and remained stable a minimum of four weeks after the completion of therapy.
• Patients must have received at least one prior chemotherapy regimen for treatment of distant metastases and achieved less than a complete response to this therapy.
• Patients must have received prior therapy with a taxane (e.g. paclitaxel) and an anthracycline (e.g. doxorubicin) as part of either adjuvant therapy or treatment of metastatic disease.
• Patients whose tumor expresses estrogen and/or progesterone receptors must have received at least one hormonal therapy (e.g. Tamoxifen) as part of either adjuvant therapy or treatment of metastatic disease.
• Patients whose tumor expresses Her2-neu must have received trastuzumab (Herceptin ) as part of either adjuvant therapy or treatment of metastatic disease.
• Patients who have undergone prior autologous stem cell transplantation are eligible for this protocol.
• Patients 18 - 75 years of age. The upper age limit was chosen in order not to be discriminatory, provided that patients meet all other eligibility criteria.
• ECOG performance status less than or equal to 2 (Karnofsky performance status greater than or equal to 60%).
• Life expectancy greater than 6 months.
• Left ventricular ejection fraction has to be greater than or equal to 45% by either MUGA or 2-D echo. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
• DLCO greater than or equal to 50% of the expected value when corrected for Hb. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
• Creatinine less than or equal to 1.5 mg/dl and a creatinine clearance greater than or equal to 50 ml/min/1.73 m(2). This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
• Direct bilirubin less than or equal to 2.5 mg/dl, SGOT less than 4x high normal value. Values above these levels may be accepted, at the discretion of the PI or study chairperson, if such elevations are thought to be due to liver involvement by malignancy. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
• Patients must be HIV-, HbsAg-, and Hepatitis C antibody negative. The high degree of immune suppression that will be used in this study may lead to the activation or progression of these viral illnesses.
• Not pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are unknown and may be harmful to the infant.

You may not qualify if:

• Active infection that is not responding to antimicrobial therapy.
• History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by principal investigator).
• History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
• History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease and will not be eligible to be a donor.
• Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per ml).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Nemoto T, Natarajan N, Bedwani R, Vana J, Murphy GP. Breast cancer in the medial half. Results of 1978 National Survey of the American College of Surgeons. Cancer. 1983 Apr 15;51(8):1333-8. doi: 10.1002/1097-0142(19830415)51:83.0.co;2-t.

  PMID: 6825053 BACKGROUND

• Smith RE, Brown AM, Mamounas EP, Anderson SJ, Lembersky BC, Atkins JH, Shibata HR, Baez L, DeFusco PA, Davila E, Tipping SJ, Bearden JD, Thirlwell MP. Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26. J Clin Oncol. 1999 Nov;17(11):3403-11. doi: 10.1200/JCO.1999.17.11.3403.

  PMID: 10550134 BACKGROUND

• Hortobagyi GN. Recent progress in the clinical development of docetaxel (Taxotere). Semin Oncol. 1999 Jun;26(3 Suppl 9):32-6.

  PMID: 10426457 BACKGROUND

• Hardy NM, Mossoba ME, Steinberg SM, Fellowes V, Yan XY, Hakim FT, Babb RR, Avila D, Gea-Banacloche J, Sportes C, Levine BL, June CH, Khuu HM, Carpenter AE, Krumlauf MC, Dwyer AJ, Gress RE, Fowler DH, Bishop MR. Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clin Cancer Res. 2011 Nov 1;17(21):6878-87. doi: 10.1158/1078-0432.CCR-11-1579. Epub 2011 Sep 26.

  PMID: 21948234 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Graft vs Host Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Daniel H Fowler, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 9, 2004
• First Posted: March 10, 2004
• Study Start: March 5, 2004
• Primary Completion: August 9, 2013
• Study Completion: August 9, 2013
• Last Updated: July 5, 2018

Record last verified: 2013-08-09

Locations

US (1)