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

Tracking Information
First Submitted Date ICMJE	June 2, 2000
First Posted Date ICMJE	January 27, 2003
Last Update Posted Date	July 5, 2017
Study Start Date ICMJE	February 2000
Actual Primary Completion Date	July 2004 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 17, 2014)	True response rate (complete response [CR] or partial response [PR]) greater than the 15% achievable with standard therapy [ Time Frame: Up to 5 years ]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 ]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 ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00005851 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 17, 2014)	Survival [ Time Frame: Up to 5 years ]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 ]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 ]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 ]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 ]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 ]Will be examined separately and reported in a descriptive manner and confidence intervals will be presented for all estimates.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Stage IV Kidney Cancer
Official Title ICMJE	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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer
Intervention ICMJE	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
Study Arms	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; Procedure: peripheral blood stem cell transplantation; Biological: therapeutic allogeneic lymphocytes; Other: laboratory biomarker analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: July 17, 2014)	11
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	July 2004 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	up to 74 Years (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00005851
Other Study ID Numbers ICMJE	1495.00; NCI-2012-00581 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 1495.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ); P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Fred Hutchinson Cancer Research Center
Study Sponsor ICMJE	Fred Hutchinson Cancer Research Center
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account	Fred Hutchinson Cancer Research Center
Verification Date	July 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP