Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Stage IV Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00005851
First received: June 2, 2000
Last updated: March 3, 2014
Last verified: March 2014

June 2, 2000
March 3, 2014
February 2000
July 2004   (final data collection date for primary outcome measure)
  • True response rate (complete response [CR] or partial response [PR]) greater than the 15% achievable with standard therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    If 6 or more out of 25 patients achieve a CR or PR, then we will be at least 80% confident that the true response rate exceeds 15% and that this approach is potentially efficacious.
  • Transplant-related mortality [ Time Frame: Within 200 days of transplant ] [ Designated as safety issue: Yes ]
  • Rate of grade IV acute GVHD [ Time Frame: Up to 90 days after last T-cell infusion ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00005851 on ClinicalTrials.gov Archive Site
  • Dose of CD3+ cells required to convert mixed to full chimeras [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented for all estimates.
  • Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.
  • Incidence of relapse [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.
  • Incidence of myelosuppression after initial PBSC infusion [ Time Frame: Up to 2 months post-transplant ] [ Designated as safety issue: Yes ]
    Defined as absolute neutrophil count [ANC] less than 500 for greater than 2 days, platelets less than 20,000 for greater than 2 days. Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.
  • Incidence of aplasia after DLI [ Time Frame: Until 2 months post-transplant ] [ Designated as safety issue: Yes ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.
  • Incidence of grades 2-4 acute GVHD after DLI [ Time Frame: Up to 90 days after last T-cell infusion ] [ Designated as safety issue: Yes ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.
  • Incidence of grades chronic extensive GVHD after DLI [ Time Frame: Up to 90 days after last T-cell infusion ] [ Designated as safety issue: Yes ]
    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented for all estimates.
Not Provided
Not Provided
Not Provided
 
Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Stage IV Kidney Cancer
Phase I/II Study of HLA-Matched Non-Myeloablative Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation as Treatment for Patients With Metastatic Renal Cell Carcinoma. A Multi-Center Trial.

The reason for doing this study is to see if cancer will respond to immune therapy after transplantation of blood stem cells (from the bone marrow) using a new kind of treatment regimen that is less toxic than that previously used for blood stem cell transplants. This type of transplant uses much less chemotherapy and radiation than standard bone marrow transplants. The treatment consists of medications that weaken the immune system so it doesn't reject the donor's marrow cells. Researchers hope that the immune cells from the donor will attack the tumor. This is called a "graft versus tumor" effect and has been seen in other types of cancer. In addition, 65 days or more after the transplant the patient may be eligible for an immune treatment that uses additional immune cells from the donor to increase the effect of the stem cells against the cancer

PRIMARY OBJECTIVES:

I. To determine whether mixed or full donor hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen.

II. To determine whether mixed chimerism can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI).

III. To evaluate potential efficacy of this approach as a treatment for metastatic renal cancer.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo low-dose total body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

IMMUNOSUPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV once daily (QD) or BID on days -3 to 35 with taper to day 56, and mycophenolate mofetil PO or IV over 2 hours thrice daily (TID) on days 0-40.

DLI: Patients with stable mixed chimerism on day 56 with no evidence of graft-vs-host disease (GVHD) may receive escalating doses of non-mobilized DLI over 30 minutes. Patients may receive up to 4 DLIs at escalating doses if there is disease progression with no evidence of GVHD.

After completion of study treatment, patients are followed up periodically for 5 years.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Radiation: total-body irradiation
    Undergo TBI
    Other Name: TBI
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
    Undergo nonmyeloablative allogeneic PBSC transplantation
  • Drug: cyclosporine
    Given PO or IV
    Other Names:
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: mycophenolate mofetil
    Given PO or IV
    Other Names:
    • Cellcept
    • MMF
  • Other: laboratory biomarker analysis
    Correlative studies
  • Procedure: peripheral blood stem cell transplantation
    Undergo nonmyeloablative allogeneic PBSC transplantation
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Biological: therapeutic allogeneic lymphocytes
    Undergo DLI
    Other Name: ALLOLYMPH
Experimental: Treatment (nonmyeloablative donor PBSC transplantation)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

IMMUNOSUPRESSION: Patients receive cyclosporine PO BID or IV QD or BID on days -3 to 35 with taper to day 56, and mycophenolate mofetil PO or IV over 2 hours TID on days 0-40.

DLI: Patients with stable mixed chimerism on day 56 with no evidence of GVHD may receive escalating doses of non-mobilized DLI over 30 minutes. Patients may receive up to 4 DLIs at escalating doses if there is disease progression with no evidence of GVHD.

Interventions:
  • Drug: fludarabine phosphate
  • Radiation: total-body irradiation
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Other: laboratory biomarker analysis
  • Procedure: peripheral blood stem cell transplantation
  • Biological: therapeutic allogeneic lymphocytes
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
25
Not Provided
July 2004   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with histologically confirmed stage IV renal cancer who have stable (including those rendered to be in remission) or progressive disease
  • Human lymphocyte antigen (HLA) genotypically identical related donor willing to undergo leukapheresis initially for collection of peripheral blood stem cells (PBSC) and subsequently for collection of peripheral blood monocytic cells (PBMC)
  • Ionized calcium level within normal limits
  • DONOR: HLA genotypically identical family member (excluding identical twins)
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
  • DONOR: Age < 75 years

Exclusion Criteria:

  • Patients who have positive serologies for human immunodeficiency virus (HIV)1 and 2, human T-lymphotropic virus (HTLV)-1
  • Patients unwilling to use contraceptive techniques during and for 12 months following treatment
  • Serum creatinine > 2.0; the Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with elevated serum creatinine following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their institutional approval; if there is not a comparable group at the institution, please contact the FHCRC principal investigator for FHCRC approval through PCC
  • Cardiac ejection fraction < 50%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
  • Diffusion capacity of carbon monoxide (DLCO) < 50% of predicted, total lung capacity (TLC) < 50%, forced expiratory volume in one second (FEV1) < 50%
  • Liver function tests including total bilirubin, serum glutamic pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 x the upper limit of normal unless due to the malignancy
  • Karnofsky score < 80
  • Brain metastasis
  • Ongoing active bacterial, viral or fungal infection
  • Pregnancy or breastfeeding
  • Patients with other active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of other non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
  • The addition of cytotoxic agents for "cytoreduction" with the exception of Gleevec (imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet criteria for donation as described in the Standard Practice Guidelines of the institution
Both
up to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00005851
1495.00, NCI-2012-00581, P01CA078902
Not Provided
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP