Phase I Study of T-Cell-Depleted Allogeneic Stem Cell Transplantation Followed By Donor Th2/Tc2 Cells, Administered After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Patients With Metastatic Breast Cancer

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Alternate Title

T-Cell-Depleted Allogeneic Stem Cell Transplantation Followed By Donor T Cells, Given After Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Metastatic Breast Cancer

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase ITreatmentClosed18 to 75NCINCI-04-C-0131

Special Category: NCI Web site featured trial



  1. Determine the safety, in terms of the incidence of acute graft-versus-host disease, and feasibility of using in vitro-generated donor T cells of Th2/Tc2 phenotype to augment a T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning in patients with metastatic breast cancer.


  1. Determine the effect of this treatment regimen on donor chimerism in these patients.
  2. Determine the effect of this treatment regimen on clinical response in these patients.
  3. Determine the progression-free and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

  • Diagnosis of stage IV breast cancer
  • Measurable disease
  • Received at least 1 prior chemotherapy regimen for treatment of distant metastases and achieved less than a complete response
    • Must have received prior therapy with a taxane (e.g., paclitaxel) and an anthracycline (e.g., doxorubicin) either as adjuvant therapy or as treatment of metastatic disease
    • If tumor expresses Her2-neu, patient must have received trastuzumab (Herceptin®) in either the adjuvant or metastatic setting
    • If tumor expresses estrogen and/or progesterone receptors, patient must have received at least 1 hormonal therapy (e.g., tamoxifen) in either the adjuvant or metastatic setting
  • CNS metastases allowed if treated and stable for at least 4 weeks after completion of therapy
  • Consenting sibling donor with 6 of 6 matching HLA antigens
  • Hormone receptor status:
    • Not specified

Prior/Concurrent Therapy:

    Biologic therapy

  • See Disease Characteristics
  • Prior autologous stem cell transplantation allowed


  • See Disease Characteristics

    Endocrine therapy

  • See Disease Characteristics


  • Not specified


  • Not specified

Patient Characteristics:


  • 18 to 75


  • Not specified

    Menopausal status

  • Not specified

    Performance status

  • ECOG 0-2


  • Karnofsky 60-100%

    Life expectancy

  • More than 6 months


  • Not specified


  • Bilirubin ≤ 2.5 mg/dL*
  • SGOT < 4 times upper limit of normal*
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative

 [Note: *Unless due to liver involvement by malignancy]


  • Creatinine ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min


  • LVEF ≥ 45% by MUGA or 2-dimensional echocardiogram


  • DLCO ≥ 50% of expected value (corrected for hemoglobin)


  • HIV negative
  • No active infection that does not respond to antimicrobial therapy
  • No history of a psychiatric disorder that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 1 year after study participation

Expected Enrollment


A total of 45 patients will be accrued for this study within 2-3 years.


This is a dose-escalation study of Th2/Tc2 cells.

  • Immunoablative induction chemotherapy: Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In order to achieve the greatest immunosuppression before transplantation, patients may receive a second course of immunoablative induction chemotherapy beginning on day 21 depending on CD4+ count.
  • Transplantation preparative regimen: Beginning 7-21 days after recovery from induction chemotherapy, patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3 before transplantation.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 12 hours beginning on day -1 and continuing until day 28, followed by a taper until day 40.
  • Allogeneic stem cell transplantation (SCT): Patients undergo T-cell-depleted allogeneic peripheral blood SCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover.
  • Donor Th2/Tc2 cell administration: Patients receive donor Th2/Tc2 cells IV on day 0 after SCT. Cohorts of 6-12 patients receive escalating doses of donor Th2/Tc2 cells until feasibility is determined. Feasibility is defined as the dose level at which no more than 6 of 12 patients experience grade II-IV acute GVHD by day 42 post-transplantation.
  • Donor lymphocyte infusion (DLI): Patients with progressive malignant disease and less than grade II acute GVHD at day 42 post-transplantation may receive DLI on days 42, 70, and 98.

Patients are followed every 2 weeks until approximately day 100 and then at 6, 9, 12, 18 and 24 months.

Published Results

Hardy NM, Mossoba ME, Steinberg SM, et al.: Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clin Cancer Res 17 (21): 6878-87, 2011.[PUBMED Abstract]

Related Publications

Bishop MR: Nonmyeloablative allogeneic hematopoietic stem cell transplantation for metastatic breast cancer. Clin Breast Cancer 4 (1): 39-45, 2003.[PUBMED Abstract]

Jung U, Foley JE, Erdmann AA, et al.: CD3/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects. Blood 102 (9): 3439-46, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Michael Bishop, MD, Protocol chair
Ph: 301-435-2764

Related Information

Featured trial article

Registry Information

Official TitleAllogeneic Breast Protocol 2: Phase I Trial Of T Cell Exchange With Th2/Tc2 Cells For Allogeneic Stem Cell Transplantation After Reduced Intensity Conditioning For Metastatic Breast Cancer
Trial Start Date2004-03-12
Trial Completion Date2008-12-31 (estimated)
Registered in ClinicalTrials.govNCT00082953
Date Submitted to PDQ2004-03-12
Information Last Verified2009-08-11

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.