Biological Therapy in Treating Women With Stage IV Breast Cancer

This study has been completed.
Information provided by (Responsible Party):
Lawrence Lum, Barbara Ann Karmanos Cancer Institute Identifier:
First received: December 7, 2001
Last updated: September 9, 2013
Last verified: September 2013

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 Intervention Phase
Breast Cancer
Biological: Aldesleukin
Biological: Sargramostim
Biological: therapeutic autologous lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • Toxicity profile [ Time Frame: Months 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: Yes ]
  • Clinical responses [ Time Frame: Months: 1, 2, 5 and 11, then every 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: October 2001
Study Completion Date: March 2013
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Aldesleukin
  • 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.

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.



Ages Eligible for Study:   18 Years and older
Genders 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
  Contacts and Locations
Please refer to this study by its identifier: NCT00027807

United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Study Chair: Lawrence G. Lum, MD, DSc Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
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.
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.

Responsible Party: Lawrence Lum, Principal Investigator, Barbara Ann Karmanos Cancer Institute Identifier: NCT00027807     History of Changes
Other Study ID Numbers: CDR0000069072, P30CA022453, 2006-130, RWMC-0635146, WSU-010307M1F, WSU-0312004412
Study First Received: December 7, 2001
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
stage IV breast cancer
recurrent breast cancer
ductal breast carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents processed this record on April 15, 2014