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: July 17, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: fludarabine phosphate
Radiation: total-body irradiation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Biological: therapeutic allogeneic lymphocytes
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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 there is at least 80% confidence 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 ]
    Defined as death before day 200 not related to progression of disease.

  • Rate of grade IV acute GVHD [ Time Frame: Up to 90 days after last T-cell infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 < 500 for > 2 days, platelets < 20,000 for > 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.


Enrollment: 11
Study Start Date: February 2000
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 mononuclear 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 glutamate 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005851

Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Colorado
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, United States, 80012
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
VA Puget Sound Health Care System
Seattle, Washington, United States, 98101
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00005851     History of Changes
Other Study ID Numbers: 1495.00, NCI-2012-00581, 1495.00, P30CA015704
Study First Received: June 2, 2000
Last Updated: July 17, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Fludarabine phosphate
Mycophenolate mofetil
Cyclosporins
Cyclosporine
Vidarabine
Fludarabine
Mycophenolic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 30, 2014