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

NCT ID: NCT00005851

Last Updated: 2019-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2018-09-27

Brief Summary

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.

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.

Conditions

Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

Given IV

total-body irradiation

Intervention Type: RADIATION

Undergo TBI

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

cyclosporine

Intervention Type: DRUG

Given PO or IV

mycophenolate mofetil

Intervention Type: DRUG

Given PO or IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

Undergo DLI

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

fludarabine phosphate

Given IV

Intervention Type: DRUG

total-body irradiation

Undergo TBI

Intervention Type: RADIATION

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Undergo nonmyeloablative allogeneic PBSC transplantation

Intervention Type: PROCEDURE

cyclosporine

Given PO or IV

Intervention Type: DRUG

mycophenolate mofetil

Given PO or IV

Intervention Type: DRUG

peripheral blood stem cell transplantation

Undergo nonmyeloablative allogeneic PBSC transplantation

Intervention Type: PROCEDURE

therapeutic allogeneic lymphocytes

Undergo DLI

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

2-F-ara-AMP; Beneflur; Fludara; TBI; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Cellcept; MMF; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell; ALLOLYMPH

Eligibility 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

• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brenda Sandmaier

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, United States

Baylor University Medical Center

Dallas, Texas, United States

VA Puget Sound Health Care System

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

NCI-2012-00581

Identifier Type: REGISTRY

Identifier Source: secondary_id

1495.00

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1495.00

Identifier Type: -

Identifier Source: org_study_id