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Biological Therapy in Treating Women With Stage IV Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00027807
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 17, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Lawrence Lum, Barbara Ann Karmanos Cancer Institute

Brief Summary:

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Aldesleukin Biological: Sargramostim Biological: therapeutic autologous lymphocytes Phase 1

Detailed Description:


  • Determine the maximum tolerated dose of armed activated T cells given in combination with interleukin-2 and sargramostim (GM-CSF) in women with stage IV breast cancer.
  • Determine the toxicity profile of this regimen in these patients.
  • Determine the clinical response and overall and progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of armed activated T cells.

Patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMCs are treated ex vivo with monoclonal antibody OKT3 to form armed activated T cells (ATC). The armed ATC are expanded for 14 days in interleukin-2 (IL-2).

Patients receive armed ATC IV over 30 minutes twice weekly for 4 weeks. Patients also receive IL-2 subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first infusion of armed ATC and continuing until 7 days after the last infusion of armed ATC.

Cohorts of 3-6 patients receive escalating doses of armed ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose.

Patients are followed at 1, 2, and 5 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for the phase I portion of this study and a total of 18-33 patients will be accrued for the phase II portion of this study within 4-6 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I Only as of 4-22-09 as Per IRB Approval Date)
Study Start Date : October 2001
Actual Primary Completion Date : September 2010
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Aldesleukin, Sargramostim & therapeutic autologous lymphocytes
Peripheral blood mononuclear cells (PBMC) for the generation of ATC will be collected using 1 or 2 phereses to obtain 8-20 × 109 PBMC for T cell expansion. The PBMC will be activated with OKT3 and expanded in IL-2 to generate from 20-320 ×109 ATC during a maximum of 14 days of culture. Three patients will be treated at each dose level. The dose levels for each infusion are: 5, 10, 20, and 40 billion. Each patient will receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encounter toxicities related to armed ATC, the dose and administration will be modified as delineated per the protocol. The patients will also receive subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250μg/m2 twice per week) will given subcutaneously to start 3 days before the 1st armed ATC infusion and ending 7 days after the last dose of armed ATC.
Biological: Aldesleukin
Subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion.
Other Names:
  • Proleukin ®
  • IL-2

Biological: Sargramostim
GM-CSF Injections will be given SQ GM-CSF (250 μg/m2/twice weekly), to start 3 days before the first ATC infusion and ending 1 week after the last ATC infusion.
Other Names:
  • LeukineTM
  • GM-CSF
  • Granulocyte-Macrophage Colony Stimulating Factor

Biological: therapeutic autologous lymphocytes
The time for armed-ATC infusions will vary from patient to patient, but the dose of armed-ATC (up to 40 billion) will be given over 30 min.

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: The dose at which dose-limiting toxicity occurs is defined as that dose at which 2 or more of 6 patients at that dose level have their infusions stopped due to toxicities or receive less than 80% of the planned dose. ]
  2. Toxicity profile [ Time Frame: Months 1, 2, 5 and 11, then every 6 months ]
  3. Clinical responses [ Time Frame: Months: 1, 2, 5 and 11, then every 6 months ]
  4. Overall survival and progression-free survival [ Time Frame: The interval from the beginning of immunotherapy to the time of death or for progression free survival it is defined as the interval from the beginning of immunotherapy to progression ]

Secondary Outcome Measures :
  1. Immune changes [ Time Frame: 1 (+ 7 days), 2 (+ 7 days), 5 months (+ 7 days), then every 6months (+ 7 days) (immune evaluations will also be performed after the 4th and 8th infusion of Her2Bi armed ATC and within 1week of the completion of HER2Bi armed ATC) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


Phase I:

  • Histologically confirmed infiltrating ductal carcinoma of the breast
  • Metastatic disease

    • Clinically asymptomatic with non-life-threatening metastases allowed
  • Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone scan, or physical examination

    • No measurable disease allowed if tumor or metastasis has been removed or successfully treated prior to study
  • No rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs and liver)
  • Stable or unstable disease for 3 months on hormonal therapy
  • Stable or unstable disease for at least 1 month after chemotherapy
  • No active brain metastases

    • Brain metastases previously treated with definitive radiotherapy and/or surgical resection allowed
  • Hormone receptor status:

    • Estrogen and progesterone receptor status known

Phase II:

  • All Phase I criteria
  • HER2/neu overexpression (2+ or 3+) by immunohistochemistry

    • Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu



  • 18 and over


  • Female

Menopausal status:

  • Not specified

Performance status:

  • Karnofsky 70-100% OR
  • ECOG 0-2

Life expectancy:

  • At least 3 months


  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 50,000/mm^3
  • Hemoglobin at least 8 g/dL


  • Bilirubin less than 1.5 times normal
  • SGOT less than 1.5 times normal


  • Creatinine no greater than 1.8 mg/dL
  • Creatinine clearance at least 60 mL/min
  • BUN no greater than 1.5 times normal


  • No myocardial infarction within the past year
  • No prior myocardial infarction with coronary symptoms requiring medication and/or depressed left ventricular function (LVEF less than 50% by MUGA)
  • No angina or coronary symptoms requiring medication and/or with depressed left ventricular function (LVEF less than 50% by MUGA)
  • No congestive heart failure requiring medical management
  • LVEF at least 50% at rest by MUGA
  • No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg)


  • FEV1, DLCO, and FVC at least 50% predicted


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No other serious medical or psychiatric illness that would preclude study participation
  • No other prior or concurrent malignancy within the past 5 years except curatively treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission


Biologic therapy:

  • See Disease Characteristics
  • Prior trastuzumab allowed for phase I


  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • Concurrent hormonal therapy for breast cancer must continue during study
  • No other concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes)


  • See Disease Characteristics


  • See Disease Characteristics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00027807

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United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
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Study Chair: Lawrence G. Lum, MD, DSc Barbara Ann Karmanos Cancer Institute
Publications of Results:
Grabert RC, Smith JA, Tiggs JC, et al.: Anti-CD3 activated T cells (ATC) armed with OKT3 x Herceptin Bispecific antibody (Her2Bi), survive and divide, and secrete cytokines and chemokines after multiple cycles of killing directed at Her2/neu+ (Her2) tumor targets. [Abstract] Proceedings of the 94th Annual Meeting of the American Association of Cancer Research 44: A-2872, 565, 2003.

Other Publications:
Lum LG, Rathore R, Colvin GA, et al.: Targeting HER2/neu tumor cells with anti-CD3 activated T cells: clinical trials and trafficking studies. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-719, 2003.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Lawrence Lum, Principal Investigator, Barbara Ann Karmanos Cancer Institute Identifier: NCT00027807    
Other Study ID Numbers: CDR0000069072
P30CA022453 ( U.S. NIH Grant/Contract )
2006-130 ( Other Identifier: Karmanos Cancer Institute )
WSU-010307M1F ( Other Identifier: Wayne State University - Human Investigation Committee )
WSU-0312004412 ( Other Identifier: Wayne State University - Human Investigation Committee )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 17, 2016
Last Verified: February 2016
Keywords provided by Lawrence Lum, Barbara Ann Karmanos Cancer Institute:
stage IV breast cancer
recurrent breast cancer
ductal breast carcinoma
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents